BackgroundHIV prevalence differs substantially between South Africa’s provinces, but the factors accounting for this difference are poorly understood.ObjectivesTo estimate HIV prevalence and incidence trends by province, and to identify the epidemiological factors that account for most of the variation between provinces.MethodsA mathematical model of the South African HIV epidemic was applied to each of the nine provinces, allowing for provincial differences in demography, sexual behaviour, male circumcision, interventions and epidemic timing. The model was calibrated to HIV prevalence data from antenatal and household surveys using a Bayesian approach. Parameters estimated for each province were substituted into the national model to assess sensitivity to provincial variations.ResultsHIV incidence in 15–49-year-olds peaked between 1997 and 2003 and has since declined steadily. By mid-2013, HIV prevalence in 15–49-year-olds varied between 9.4% (95% CI: 8.5%–10.2%) in Western Cape and 26.8% (95% CI: 25.8%–27.6%) in KwaZulu-Natal. When standardising parameters across provinces, this prevalence was sensitive to provincial differences in the prevalence of male circumcision (range 12.3%–21.4%) and the level of non-marital sexual activity (range 9.5%–24.1%), but not to provincial differences in condom use (range 17.7%–21.2%), sexual mixing (range 15.9%–19.2%), marriage (range 18.2%–19.4%) or assumed HIV prevalence in 1985 (range 17.0%–19.1%).ConclusionThe provinces of South Africa differ in the timing and magnitude of their HIV epidemics. Most of the heterogeneity in HIV prevalence between South Africa’s provinces is attributable to differences in the prevalence of male circumcision and the frequency of non-marital sexual activity.