BACKGROUND: Buruli ulcer is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear. METHODS: This was a retrospective study of data collected at the Akonolinga District Hospital, Cameroon, from January 1, 2002 to March 27, 2013. Human immunodeficiency virus prevalence among BU patients was compared with regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients and according to CD4 cell count strata in the latter group. Buruli ulcer time-to-healing was assessed in different CD4 count strata, and factors associated with BU main lesion size at baseline were identified. RESULTS: Human immunodeficiency virus prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). Individuals who were HIV positive had a more severe form of BU, with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (β-coefficient, -0.50; P = .015; 95% confidence interval [CI], -0.91-0.10). Buruli ulcer time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm(3) (hazard ratio, 2.39; P = .001; 95% CI, 1.44-3.98). CONCLUSION: Patients who are HIV positive are at higher risk for BU. Human immunodeficiency virus-induced immunosuppression seems to have an impact on BU clinical presentation and disease evolution.