The clinical presentations and outcomes of cryptococcal meningitis (CM) may be associated with the cryptococcal species causing the infections. To evaluate clinical differences between CM caused by C. neoformans and Cryptococcus gattii, we examined outcomes in HIV-infected adults with CM admitted to Princess Marina Hospital in Gaborone, Botswana. Among HIV-infected adults with CM, we found that 29 of 96 (30%) patients were infected with C. gattii, but species type was not associated with in-hospital mortality [mortality for C. gattii: 5 of 29 (17%) vs C. neoformans: 13 of 67 (19%); OR = 0.87 (95% CI 0.28 to 2.70)]. The proportion of C. gattii infection among this HIV-infected cohort in Botswana is the highest reported to date, but we found no difference between C. gattii and C. neoformans in clinical presentation or in-hospital mortality.