© The authors, 2026

Introduction

Surgical removal of impacted mandibular third molars is one of the most frequent procedures performed in oral and maxillofacial surgery. Despite advances in technique and perioperative care, postoperative sequelae such as pain, swelling, and alveolar osteitis (“dry socket”) remain common and can adversely affect patient recovery and satisfaction. Local infection and inflammatory reactions following tissue trauma largely cause these complications [1]. Therefore, reducing postoperative inflammation and bacterial contamination is a continuing clinical priority.

Povidone-iodine (PVP-I) is a water-soluble complex of iodine with polyvinylpyrrolidone that gradually releases free iodine, producing potent bactericidal, virucidal, and fungicidal effects while maintaining low cytotoxicity. In surgical disciplines, PVP-I is widely used as a skin and mucosal antiseptic. A number of studies have also indicated its hemostatic and anti-edematous effects, which may enhance postoperative healing outcomes [2–4].

In oral surgery, normal saline remains the standard intraoperative irrigant for cooling the surgical site and removing debris. However, its lack of antiseptic or anti-inflammatory action may limit its effectiveness in preventing postoperative complications. Previous small clinical studies have reported that irrigation with PVP-I may reduce postoperative edema and dry socket incidence compared with saline, yet evidence from well-designed randomized controlled trials remains limited and inconsistent [5–7].

The present randomized controlled trial aimed to evaluate whether intraoperative irrigation with 1% PVP-I solution reduces postoperative pain, swelling, and incidence of dry socket following surgical removal of impacted mandibular third molars compared with conventional saline irrigation.

Materials and methods

Study design and ethics

A randomized, controlled, parallel-group clinical trial was conducted between January and December 2024. The study protocol complied with the principles of the Declaration of Helsinki and was approved by the university's board. Written informed consent was obtained from all participants prior to enrollment.

Participants

The study enrolled a total of 162 apparently healthy individuals aged 18 to 60 yr who required surgical removal of impacted mandibular third molars. All participants were considered medically fit for elective oral surgery, corresponding to ASA Physical Status I or II. Patients were included if they had no history of systemic illness or previous eventful extractions. Exclusion criteria were a known allergy or hypersensitivity to povidone-iodine or povidone-containing agents, long-term use of anticoagulant or nonsteroidal anti-inflammatory drugs, pregnancy or lactation, and the presence of any active oral or systemic infection at the time of surgery.

Sample size calculation

Sample size was calculated using G*Power 3.1 software based on a two-tailed t-test with 80% power and α = 0.05, assuming a medium effect size (Cohen’s d = 0.5) derived from prior studies. The minimum required sample was 128 patients (64 per group); to compensate for potential dropouts, 162 participants were recruited.

Randomization and blinding

Participants were randomly assigned in a 1:1 ratio to either the PVP-I group or the saline control group using a computer-generated random sequence (SPSS random number generator). Allocation was concealed in sequentially numbered, opaque, sealed envelopes opened at the time of surgery.

While the surgeon could not be blinded to the irrigant, the postoperative assessor and patients were blinded to group assignment to minimize bias.

Surgical procedure

All surgeries were performed by the same oral surgeon using a standardized technique under local anesthesia (2% lidocaine with 1:100,000 epinephrine). After flap reflection and bone removal, the tooth was sectioned when necessary.

• Study group: irrigation performed with 1% (w/v) PVP-I in 0.9% sodium chloride solution.

• Control group: irrigation performed with sterile 0.9% sodium chloride solution only.

Irrigation was applied continuously during bone cutting and socket debridement. Following tooth removal, sockets were rinsed with the allocated solution, and the wound was closed using 3-0 silk sutures.

All patients received identical postoperative instructions and medication (oral ibuprofen 400 mg every 8 h for 3 days and amoxicillin 500 mg every 8 h for 5 days).

Outcome measures

Patients were evaluated on postoperative days 2 and 7 by an examiner blinded to treatment allocation.

• Pain was assessed using a 10-cm Visual Analogue Scale (VAS), with 0 = no pain and 10 = worst imaginable pain.

• Swelling was measured subjectively as the presence or absence of visible facial edema compared with the contralateral side and confirmed by linear facial measurements (tragus-pogonion and gonion-lateral canthus distances).

• Dry socket (alveolar osteitis) was diagnosed clinically by the presence of severe throbbing pain, exposed alveolar bone, and absence of clot within 2–5 days post-extraction.

Adverse reactions, such as allergy or delayed healing, were recorded.

Statistical analysis

All data were entered into SPSS version 24.0 (IBM Corp., Armonk, NY, USA).

Continuous variables were expressed as mean ± standard deviation (SD).

• Intergroup differences for pain and swelling scores were analyzed using the independent-samples t-test (for normally distributed data) or the Mann–Whitney U test (for non-parametric data).

• Categorical variables such as dry socket incidence were analyzed using the chi-square test or Fisher’s exact test, as appropriate.

• Statistical significance was set at p < 0.05.

• Effect sizes (Cohen’s d) and 95% confidence intervals (CI) were calculated for primary outcomes.

Results

A total of 162 patients completed the study (66 males and 96 females; mean age ± SD = 28 ± 6.4 yr; range 17–42 yr). All participants tolerated the procedures well, and no adverse reactions or allergic responses were recorded (Fig. 1).

Fig. 1 Study flowchart.

Pain

Mean postoperative pain scores were significantly lower in the PVP-I group than in the saline control group at both evaluation points. On postoperative day 2, the median pain score on the VAS was 2.0 (IQR 1–4) for the PVP-I group and 5.0 (IQR 3–7) for the saline group (Mann–Whitney U = 2208.0, Z = −4.14, p = 0.01). On day 7, scores were 0 (IQR 0–1) and 2 (IQR 1–3), respectively (U = 2563.0, Z = −3.27, p = 0.02). The mean reduction in pain scores from day 2 to day 7 was greater in the PVP-I group (−2.1 ± 0.9) than in the controls (−1.3 ± 1.1, p < 0.01).

Swelling

A statistically significant difference in postoperative swelling was observed between groups across all time points. Facial edema was present in 12.3% of patients in the PVP-I group compared with 87.7% in the saline group (χ² = 49.3, p < 0.001). Swelling typically subsided by day 7 in both groups but resolved earlier and more completely among those irrigated with PVP-I.

Dry socket

In the PVP-I group, 5 out of 81 patients (6.2%) developed dry socket, while in the saline group, 16 out of 81 patients (19.7%) did. This is a significant decrease in the number of cases (χ² = 6.61, p = 0.01). The relative risk reduction for dry socket with PVP-I irrigation was 68% (95% CI = 18–87%), corresponding to a number needed to treat (NNT) of approximately 8 patients to prevent one case, as shown in Table I.

Summary of findings

Overall, irrigation with 1% PVP-I resulted in statistically and clinically significant reductions in postoperative pain, swelling, and dry socket occurrence when compared with saline irrigation.

Discussion

The present randomized controlled trial demonstrated that intraoperative irrigation with 1% povidone-iodine (PVP-I) significantly reduced postoperative pain, swelling, and incidence of alveolar osteitis following surgical extraction of impacted mandibular third molars compared with conventional saline irrigation. These results add to the growing body of evidence that PVP-I is a simple, cheap, and safe addition to oral surgery that can improve postoperative outcomes.

The broad-spectrum antimicrobial, anti-edematous, and hemostatic properties of PVP-I account for the observed benefits. It works by releasing free iodine, which gets through the cell walls of microbes and oxidizes proteins and nucleotides. This kills microbes quickly with little chance of them becoming resistant [1,2]. In addition to its antimicrobial role, PVP-I reduces local inflammation and exudation, stabilizes the clot, and promotes angiogenesis and fibroblast proliferation—all of which contribute to reduced pain, edema, and socket complications [3–5]. Kumar et al. and Arakeri et al. demonstrated that PVP-I exhibits hemostatic effects by enhancing platelet aggregation and vasoconstriction, and also attenuating local edema via inhibition of vascular permeability [2, 3].

Our results are consistent with previous clinical studies indicating that povidone-iodine is effective in reducing postoperative complications following mandibular third-molar surgery. Hasheminia et al. demonstrated that the use of a 1% povidone-iodine (Betadine) mouthwash significantly reduced the incidence of alveolar osteitis after surgical extraction of impacted mandibular third molars, highlighting its role in dry socket prevention [6]. In addition, Mohammed et al. reported that intraoperative povidone-iodine irrigation was associated with significant reductions in postoperative edema and improved hemostasis compared with conventional irrigation methods [7]. Similarly, in a pilot split-mouth randomized study, Hashemi et al. showed that low-concentration povidone-iodine irrigation resulted in fewer postoperative complications, including reduced pain and swelling, compared with control irrigation [8]. A meta-analysis by Shi et al. confirmed that PVP-I irrigation effectively reduces surgical site infections across multiple surgical fields [9]. Collectively, these findings support the present results and reinforce the clinical value of povidone-iodine as an effective adjunct for minimizing postoperative morbidity after third-molar extraction.

Although chlorhexidine remains one of the most extensively studied antiseptics in oral surgery, accumulating evidence suggests that povidone-iodine provides comparable clinical benefits without the mucosal irritation, taste disturbance, or tooth staining commonly associated with chlorhexidine [10–13]. A recent randomized controlled trial by Shahraki et al. (2025) directly compared chlorhexidine, povidone-iodine, and hydrogen peroxide irrigation following mandibular third-molar surgery and demonstrated significant reductions in postoperative pain and swelling in patients receiving povidone-iodine irrigation compared with saline and hydrogen peroxide controls [14].

These findings are further supported by contemporary high-quality evidence. A large systematic review and network meta-analysis by Groenen et al. (2024) confirmed that antiseptic wound irrigation, including povidone-iodine–based solutions, significantly reduces postoperative inflammatory complications and surgical site infections across multiple surgical specialties, underscoring the continued relevance of povidone-iodine in modern surgical practice [15]. In parallel, foundational evidence on surgical site infection prevention highlights the importance of appropriate antiseptic selection and application technique in optimizing postoperative outcomes [16]. More recently, an updated meta-analysis and trial sequential analysis by Yang et al. (2025) demonstrated that both povidone-iodine and chlorhexidine are effective for surgical site infection prevention, with no clear superiority when appropriately applied, suggesting that agent selection should be guided by safety profile, tolerability, and clinical context [17].

Collectively, these studies—spanning both established and recent high-level evidence—support the present findings and reinforce the role of povidone-iodine as an effective, well-tolerated, and clinically relevant intraoperative irrigant for reducing postoperative morbidity after third-molar surgery.

The significantly lower rate of alveolar osteitis in the PVP-I group may relate to its capacity to suppress fibrinolysis and maintain clot stability. By controlling local infection and limiting bacterial protease activity, PVP-I reduces early clot disintegration, thereby decreasing the risk of dry socket formation [15,16,18]. Moreover, its sustained antiseptic effect may enhance socket healing by promoting a favorable microenvironment for tissue regeneration [19].

The study has several strengths, including a randomized controlled design, standardized surgical protocol, and blinding of postoperative assessors. However, several limitations should be acknowledged. Complete surgeon blinding was not feasible due to the visible difference between irrigants, which may have introduced performance bias. In addition, variations in impaction depth and surgical difficulty were not categorized, and the follow-up duration was limited to 7 days, restricting evaluation of late postoperative outcomes. Furthermore, the study was not powered to perform subgroup analyses based on age, sex, or patient-related health factors, which may influence postoperative pain perception, inflammatory response, and healing patterns. Consequently, potential effect modification by these variables could not be reliably assessed. Future multicenter randomized studies with larger sample sizes, standardized surgical difficulty indices, stratified subgroup analyses, and extended follow-up periods are warranted to validate these findings and to determine the optimal concentration and application protocol of povidone-iodine irrigation.

Clinically, 1% PVP-I represents a readily available and inexpensive adjunct that can improve patient comfort and accelerate recovery after third-molar surgery. Given its excellent safety profile and broad antiseptic coverage, its integration into routine oral surgical protocols could reduce postoperative morbidity and healthcare costs, particularly in resource-limited settings.

Conclusion

Intraoperative irrigation with a 1% povidone-iodine solution significantly diminished postoperative pain, swelling, and the occurrence of dry socket following the surgical extraction of impacted mandibular third molars, in contrast to saline irrigation. These results support the potential value of PVP-I as an effective and economical adjunct in oral surgical practice.

Given its broad antimicrobial activity, favorable safety profile, and low cost, povidone-iodine may represent a practical option for improving postoperative outcomes in routine third molar surgery.

Future multicenter, double-blinded randomized trials with larger sample sizes and standardized outcome definitions are recommended to confirm these findings and determine the optimal concentration and application method for PVP-I irrigation.

Funding

No funding was provided for the research.

Conflicts of interest

The authors declare no conflict of interest in regards to this article.

Data availability statement

The current study's datasets are available upon reasonable request from the corresponding author.

References

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	Fig. 1 Study flowchart.
In the text