Allergic fungal rhinosinusitis (AFRS) is the most common form of fungal sinus disease. Its recurrence rate is high despite numerous strategies to prevent it. We conducted a study to assess the effect of systemic and topical antifungal agents-both separately and in combination-in preventing recurrence of AFRS following functional endoscopic sinus surgery (FESS). Our initial study population was made up of 50 adults who were diagnosed with AFRS by clinical, radiologic, histopathologic, and laboratory workup and who subsequently underwent FESS. Postoperatively, these patients were randomized into 5 different treatment groups matched for sex, age, and socioeconomic status. Four of the groups received a different antifungal regimen in addition to convenient medical treatment (CMT), while a fifth group served as a control. The antifungal regimens included oral itraconazole (group A), fluconazole nasal spray (group B), combined oral itraconazole and nasal fluconazole (group C), and irrigation with a fluconazole solution through the nasal fossa (group D); the group of 10 controls (group E) received CMT only. A total of 41 patients were available for follow-up (9 mo maximum). Recurrence rates in the 5 groups were 66.7, 10.0, 14.3, 28.6, and 75.0%, respectively. Based on our findings, we conclude that treatment with topical fluconazole as either a nasal spray or an irrigation solution can significantly reduce the rate of recurrence of AFRS after FESS.