Objective: Evaluate the effect of antiretroviral therapy (ART) on South African HIV patients’ economic well being, as indicated by symptoms, normal activities, employment, and external support, during the first 5 years on treatment. Methods: Prospective cohort study of 879 adult patients at public or nongovernmental clinics enrolled before ART initiation or on ART less than 6 months and followed for 5.5 years or less. Patients were interviewed during routine clinic visits. Outcomes were estimated using population-averaged logistic regression and reported as proportions of the cohort experiencing outcomes by duration on ART. Results: For patients remaining in care, outcomes improved continuously and substantially, with all differences between baseline and 5 years statistically significant (P