Chronic rhinosinusitis (CRS) is believed to be the result of an exaggerated reaction to fungi in the nasal mucosa, and topical amphotericin B (AMB) is a commonly used treatment. The purpose of this study was to perform a meta-analysis of high-quality comparative studies to examine the efficacy of topical AMB for the treatment of CRS. A search was conducted of Medline, Cochrane, EMBASE, and ISI Web of Knowledge until December 31, 2013 using combinations of the search terms chronic rhinosinusitis, human, treatment, antibiotics, nasal irrigation, nebulized, nasal lavage, sinonasal rinses, and antimicrobials. Inclusion criteria were (1) comparative studies, (2) a diagnosis of CRS or chronic sinusitis, and (3) the intervention was a topical antifungal. The primary outcome measure was quality of life (QOL), and the secondary was nasal endoscopy score. Of 235 article initially identified, five randomized controlled trials were included in the meta-analysis. Analysis of four studies with complete QOL data found no difference between treatment and placebo groups [standard difference in means 0.78, 95 % confidence interval (CI) -0.25 to 1.81, P = 0.138]. Analysis of four studies with complete nasal endoscopy score data found no difference between the treatment and placebo groups (standard difference in means 0.34, 95 % CI -0.08 to 0.76, P = 0.117). AMB is not more effective than placebo in improving QOL or nasal endoscopy scores in patients with CRS.