A prospective observational study was conducted for 18 months to analyze the mycological profile of clinically suspected cases of fungal rhinosinusitis requiring endoscopic sinus surgery and test antifungal susceptibility of the isolates according to Clinical and Laboratory Standards Institute guidelines. Per-operative biopsies (n = 126) from 106 patients were processed by standard mycological procedures. Out of 126 samples, 59 (46.83 %) had fungal elements on KOH mount examination. Fungal growth was obtained in 76 (60.32 %) samples, of which single fungal organism was isolated in 68 samples and more than one fungal species in eight samples. The most common isolates belonged to the genus Aspergillus (n = 53, A. flavus being most common) followed by mucormycetes (9), Candida species (7), Penicillium species (5), Alternaria species (5), Fusarium species (1), Curvularia species (1) and black yeast (1). Two hyaline septate fungal isolates could not be identified. Aspergillus species were susceptible to amphotericin B (n = 46), itraconazole (n = 48), voriconazole (n = 52), posaconazole (n = 53), caspofungin (n = 51), anidulafungin (n = 53) and micafungin (n = 53). All mucormycetes isolates (n = 9) were susceptible to amphotericin B, posaconazole and itraconazole. Filamentous non-Aspergillus, non-mucormycetes isolates (n = 15) were susceptible to amphotericin B (n = 12), itraconazole (n = 13), voriconazole (n = 15), posaconazole (n = 15) and echinocandins (n = 15). Amongst the 07 Candida species, 05 isolates of Candida tropicalis were susceptible to amphotericin B, posaconazole, echinocandins and 5-flucytosine; one isolate of Candida albicans had the same susceptibility but was resistant to 5-flucytosine also, and one strain of Candida species was susceptible to all the nine antifungal drugs.