Introduction: Neuromeningeal cryptococcosis (NMC) is a severe and fatal opportunistic infection. Lethality is higher in the absence of treatment, especially in HIV co-infection. The objective of the present study was to determine the prevalence, epidemiological, clinical, biological, and therapeutic features as well as the outcome of NMC in HIV-infected patients. Methods: This is a retrospective study of 108 cases of NMC diagnosed in HIV-infected patients. Data were collected over 36 months (from January 2015 to December 2017) at the HIV/AIDS Center of Excellence in Lubumbashi (Democratic Republic of the Congo). Results: The overall prevalence of NMC is 2.5%. The mean age of the patients was 41.5±13.1 years, with 72.2% aged less than 50 years. The main clinical symptomatology was headache (100%) and fever (100%). The main cytochemical CSF abnormalities were hyperproteinorachia (91.9%), hypoglycorachia (94%) and hyper-lymphocytosis (98.2%). The mean CD4 count was 168.7±137.1/mm3. All patients were treated with fluconazole. The overall lethality was 43.5%. Conclusion: NMC is a serious opportunistic infection in HIV-infected patients, and the case fatality rate remains unacceptable. Management of NMC in HIV-positive patients requires early diagnosis, increased access to antiretrovirals and prompt initiation of appropriate treatment.