AIDS-associated Kaposi sarcoma (AIDS-KS) is the most common HIV-related malignancy. The majority of cases are found in sub-Saharan Africa. This retrospective cohort study describes characteristics of patients with AIDS-KS and factors associated with mortality in an antiretroviral treatment (ART) program in rural Malawi. Of 11 122 patients enrolled on ART, 830 (7%) had AIDS-KS. Patients with AIDS-KS were more likely to be lost to follow-up (22% versus 14%, P < 0.001) and showed a higher mortality (22% versus 10%, P < 0.001) compared to patients without AIDS-KS. A CD4 count ≤150 cells/μl, advanced stage AIDS-KS, and absence of bleomycin chemotherapy were associated with increased mortality. Earlier diagnosis and improved treatment of AIDS-KS are urgently needed in order to reduce mortality.