Tehran University of Medical Sciences (TUMS) Academic Journal of Surgery 2423-3218 8 3 2025 12 22 101 105 elnaz mokhtari Elnaz Mokhtari, ENT Resident, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2025 06 04 Introduction: Frontal sinus ostium stenosis is a common postoperative challenge in endoscopic sinus surgery, potentially leading to disease recurrence. Imiquimod is an immunomodulatory agent with anti-inflammatory and antifibrotic properties, recently gaining attention in experimental studies. Objective: To evaluate the safety of low-dose topical imiquimod cream in reducing the rate of frontal sinus ostium stenosis following endoscopic sinus surgery. Methods: This pilot randomized intra-patient controlled clinical trial was conducted on 20 patients with CRSwNP. Each patient underwent bilateral Draf 2a surgery. One frontal sinus was randomly assigned to receive Gelfoam impregnated with 5% imiquimod cream, with applications repeated in the second and fourth postoperative weeks. The contralateral side served as the control. Patients were assessed at week 4 and month 3 postoperatively via endoscopic and CT imaging. Endoscopic scores were based on the DIP system, and the STDR ratio was evaluated using 3D CT reconstruction. Data analysis was performed using paired t-tests and Wilcoxon tests at a significance level of 0.05. Results: At three months post-surgery, STDR was significantly lower on the intervention side (p < 0.05), indicating reduced soft tissue density and opacification. Endoscopic evaluation also showed a marked improvement in polyp and inflammation scores on the treated side. No significant differences were observed at one month. No major local or systemic adverse effects were reported. Conclusion: Topical application of low-dose imiquimod cream after endoscopic sinus surgery may effectively reduce inflammation, discharge, polyp formation, and opacification in the frontal sinus, and may be considered a safe preventive option for ostium stenosis. Larger trials are recommended to confirm these findings https://ajs.tums.ac.ir/index.php/ajs/article/view/317