Cryptococcosis in HIV-seronegative patients is rarely reported from India. This prospective study was conducted to look for cryptococcal meningitis in HIV-seronegative individuals and compare their laboratory features to cryptococcal meningitis in HIV-seropositive patients. Cerebrospinal fluid was collected from 153 suspected cases of meningitis and subjected to India ink preparation, antigen detection, and culture. Nineteen samples tested positive for Cryptococcus neoformans infection. Seventeen and two patients were HIV reactive and nonreactive, respectively. In vitro susceptibility of C. neoformans isolates to fluconazole and amphotericin B was performed using standard broth microdilution method and E-test. Eighteen strains were susceptible to amphotericin B, while fluconazole was reported susceptible in 15 strains. Hence, index of suspicion of C. neoformans infection as possible cause of meningitis must be maintained even in HIV-negative patients. Use of amphotericin B for treating C. neoformans meningitis should be restricted to prevent any increase in resistance.