Abstract: Objective To determine the genotypes and in vitro antifungal susceptibility of Cryptococcus strains isolated from Sichuan Province. Methods Ninety two clinical isolates of Cryptococcus spp. were collected from West China Hospital. Genotyping of the URA5 gene was accomplished by restriction fragment length polymorphism. The minimum inhibitory concentrations (MIC) of the isolates to 5 antifungals, including amphotericin B, flucytosine, fluconazole, itraconazole and voriconazole were determined by agar-based E-test method. The MIC₅₀ and MIC₉₀ were calculated based on MICs. Results Among the 92 clinical isolates, 91 were molecular type VNⅠ and one was VGⅡ. The susceptibility range, MIC₅₀ and MIC₉₀ of the isolates to five antifungals were as follows: (<0.002-2) μg/mL, 0.19 μg/mL and 0.75 μg/mL for amphotericin B; (0.5->32) μg/mL, 4 μg/mL and 8 μg/mL for flucytosine; (0.5-32) μg/mL, 3 μg/mL and 8 μg/mL for uconazole; (0.064-2) μg/mL, 0.5 μg/mL and 1.5 μg/mL for itraconazole; (0.004-0.19) μg/mL, 0.047 μg/mL and 0.094 μg/mL for voriconazole. Three (3.3%) isolates were resistant to amphotericin B, 4(4.3%) to flucytosine and 25(27.2%) to itraconazole. No isolate was resistant to fluconazole and all isolates were susceptible to voriconazole. The isolate Cryprococcus gattii was resistant to flucytosine, while S-DD was resistant to fluconazole. There were significant differences in the MICs of the strains isolated from different periods. The MICs of the isolates to amphotericin B and flucytosine increased over time. Conclusion VNI molecular type is the major genotype of Cryprococcus in Sichuan. All the agents have good in vitro activities against the tested strains except itraconazole. A few stains are resistant to amphotericin B and flucytosine.