BACKGROUND: Recurrence of nasal polyposis following surgical intervention is very common. Antifungal therapy has been an appealing alternative to reduce its recurrence and severity. Early studies showed definite positive response, but recent studies have raised doubts about its efficacy in treatment of polyposis. METHODS: This prospective case-control clinical trial was conducted on 50 patients suffering from nasal polyposis in Isfahan University of medical sciences. All patients underwent functional endoscopic sinus surgery. CT scanning of paranasal sinuses was done preoperatively and 6 months postoperatively to stage the disease. Patients were assigned to two groups: amphotericine B group were instructed to irrigate the nasal cavity with a solution of amphotericine B, while the normal saline group used the physiologic normal saline for 6 months. RESULTS: 68% of patients in Normal saline and 84% of cases in amphotericine B group reported history of allergies. In amphotericine B group, stage of the disease improved in 84% of patients and remained unchanged in the rest. In normal saline group, imaging stage improved in 22 patients and remained unchanged in 3. The two cohorts were compared for reduction in imaging stage and no significant difference was found between them. CONCLUSIONS: This study showed no benefits for topical amphotericin B solution over normal saline. It might be better to retreat to the traditional normal saline nasal douching following functional endoscopic sinus surgery in the treatment of polyposis.