| Summary: | <b>Background:</b> Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. <b>Methods:</b> This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged ≥15 years were enrolled onto the study. <b>Results</b>: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age < 45 years (OR 8.70, 95% CI 1.78–42.62), white blood cells < 5000 cells/cu.mm. (OR 7.18, 95% CI 1.45–35.61), and presence of fungemia (OR 5.86, 95% CI 1.17–42.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, <i>p</i>-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55–19.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42–6.10), infection caused by members of <i>C. gattii</i> species complex (HR 4.19, 95% CI 1.39–12.62), and anemia (HR 3.17, 95% CI 1.17–8.59). <b>Conclusions:</b> Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.
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