Adhesions after endoscopic sinus surgery (ESS) are a potential cause of surgical failure. Mitomycin-C (MMC) is recently proposed as a solution for these adhesions. This study was performed to investigate the effect of Mitomycin C in reducing scar formation and adhesion in the nasal mucosa after endoscopic nasal surgery. This double blind randomized clinical trial study was performed on 37 patients with bilateral chronic rhinosinusitis. At the end of ESS, randomly impregnated mesh with MMC was placed in one side and another mesh impregnated with saline in the opposite side for 5 minutes. Patients were followed at least for three months, and the results of diagnostic endoscopy were recorded. Post operative adhesion occurred in 12 (32.4%) patients (2 bilateral/10 unilateral). Among total of 14 adhesions, 4 (10.8%) were in the MMC side and 10 (27%) in the control side. This differences was close to statistically significant (P=0.058). MMC may reduce adhesions after ESS, but further studies with different doses, sample size and frequent use of topical MMC is recommended.