BACKGROUND: Noncommunicable diseases are common among chronically infected patients with HIV in the developed world, but little is known about these conditions in African cohorts. We assessed the epidemiology of metabolic syndrome among young South African women during the first 3 years after HIV acquisition. METHODS: A total of 160 women were followed prospectively in the CAPRISA 002 Acute Infection study. Metabolic syndrome was defined as a constellation of hyperlipidemia, hypertension, hyperglycemia/diabetes, and abdominal obesity. Time trends were assessed using generalized estimation equation models. RESULTS: Median age was 24 years and body mass index 27 kg/m. Prevalence of metabolic syndrome at infection was 8.7% increasing to 19.2% over 36 months (P = 0.001). The proportion of women with body mass index >30 kg/m increased from 34.4% to 47.7% (P = 0.004), those with abnormal waist circumference and elevated blood pressure increased from 33.5% to 44.3% (P = 0.060) and 23.8% to 43.9% (P < 0.001), respectively. Incidence of metabolic syndrome was 9.13/100 person-years (95% CI: 6.02 to 13.28). Predictors of metabolic syndrome were age (per year increase odds ratio (OR) = 1.12; 95% CI: 1.07 to 1.16), time postinfection (per year OR = 1.47; 95% CI: 1.12 to 1.92), family history of diabetes (OR = 3.13; 95% CI: 1.71 to 5.72), and the human leukocyte antigen (HLA)-B81:01 allele (OR = 2.95; 95% CI: 1.21 to 7.17), whereas any HLA-B57 or B*58:01 alleles were protective (OR = 0.34; 95% CI: 0.15 to 0.77). HIV-1 RNA (OR = 0.89; 95% CI: 0.62 to 1.27) and CD4 count (OR = 1.03; 95% CI: 0.95 to 1.11) did not predict metabolic syndrome. CONCLUSIONS: The high burden of metabolic conditions in young South African HIV-infected women highlights the need to integrate noncommunicable disease and HIV care programs. Interventions to prevent cardiovascular disease must start at HIV diagnosis, rather than later during the disease course.