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Little is known about how antiretroviral therapy (ART) affects patients' economic activities in resource-constrained settings. This study examined the association of ART with functional impairment, symptom prevalence, and employment during the first 6 months on therapy.Interviews were conducted with 453 patients receiving pre-ART care and 427 patients on ART for 1–6 months in South Africa.Pre-ART subjects were almost twice as likely to report being functionally impaired (unable to perform primary normal activity) in the previous 5-day work week [adjusted odds ratio (OR) 1.97; 95% confidence interval (CI) 1.46–2.66], with a mean of 1.61 impaired days for pre-ART subjects versus 0.87 days for ART subjects (P < 0.0001). Pre-ART subjects were more likely to report fatigue (OR 2.84; 95% CI 2.10–3.84), pain (OR 2.06; 95% CI 1.53–2.76), and nausea (OR 1.61; 95% CI 1.13–2.28) in the previous week and feeling unwell physically (OR 1.71; 95% CI 1.27–2.32), feeling depressed (OR 1.42; 95% CI 1.04–1.95) or resting (OR 1.52; 95% CI 1.12–2.07) on the previous day. The prevalence of pain, fatigue, skin problems, and resting exceeded 40% in both groups. Employed subjects on ART for 3–6 months reported 3 days less health-related absenteeism per month than those on ART less than 3 months (P = 0.0353).Patients who have initiated ART reported significantly less functional impairment, fewer symptoms, and better work performance than those who had not yet started treatment. The prevalence of some impairment, symptoms, and absenteeism remained high, however.