Background Although the burden of Kaposi sarcoma (KS) is fast increasing among HIV-infected populations, there is still critical lack of knowledge on its related driving factors in Cameroon. This study purposed to determine risk factors for KS in HIV-infected patients living in Yaounde, Cameroon. Methods This was a 1:3 case-control study nested on a retrospective cohort study, carried-out over a period of 16 years at the Yaounde Central Hospital, Cameroon. Cases were HIV-infected patients, diagnosed with KS after histological confirmation. Controls were HIV-infected patients, naive of KS and paired to cases through age and sex. Logistic regression analyses served to identify risk factors for KS. Results Of 14,220 files reviewed, 316 cases of KS (2.2%) were identified. We included 266 cases (55% males), to whom 798 controls were paired. The mean age of patients was 37.7 ± 9.6 years. Results of multivariable logistic regression analysis identified diabetes [adjusted odds ratio (aOR) 2.9, 95%CI: 1.3–7.7; p = 0.028] and HIV-related prurigo [aOR 0.3, 95%CI: 0.1–0.7; p = 0.010] as factors impacting significantly KS occurrence in this study. Conclusion KS is frequent among our HIV-infected patients. Those having diabetes seem at increased odds of developing KS.