Chronic Rhinosinusitis (CRS) is the most common chronic disease that is refractory to treatment. Authors suggested that a fungus mediated process is the primary cause of CRS with and without polyps through a local immune response to the fungus present within the mucous.On the basis of these observations, topical antifungal treatment should eradicate the fungus from the mucous and improve the course of the disease. Thus, reduction of the fungus in the sinus and nasal cavities by means of topical antifungal treatment might reduce both the immune and the inflammatory responses to the organisms, and might clinically benefit patients with CRS.Objective: This study was designed to evaluate the efficiency of topical anti fungal drug Amphotericin B in the treatment of patients with refractory CRS as compared to endoscopic sinus surgery.Methods: Forty patients suffering from CRS that is refractory to ordinary medical treatment were enrolled in this study. Patients were selected among those attending the ENT outpatient clinic of Kasr El-Aini hospital Cairo University. Patients were then divided into two groups; randomly, according to the method of treatment used, and each group included 20 patients. These were:Group A: Treated with intranasal Amphotericin B.Group B: Treated with functional endoscopic sinus surgery (FESS).Patients of both groups underwent both subjective assessment by Lund and Mackay, 1993; the visual analogue scale (VAS) and objective assessment by endoscopic and CT scoring systems of the same authors pre-treatment as well as 3 months post-treatment.Results: Group A: Sixteen (80%) patients reported variable improvement in their symptoms; however, none of them reported complete recovery. There were 4 (20%) patients who reported no improvement. None of our patients experienced further worsening of their symptoms. There was statistically highly significant difference between the pre and post treatment endoscopy score, as well as the CT score.Group B: Seventeen 17 patients (85%) had more than 50% reduction of their symptoms score, 13 (65%) patient had more than 50% improvement in their endoscopic scorring, on the other hand 18 (90%) patient had more than 50% improvement of their CT score.Conclusion: Treatment with topical intranasal amphotericin B solution is found to be safe, convenient and effective treatment for patients with CRS without polyposis that is refractory to other therapies. Thus, the intranasal antifungal treatment seems to be a promising treatment for patients with CRS refractory to other therapies.