To identify factors that influence adherence to short-course antiretroviral (ARV) prophylaxis by pregnant women and mothers participating in the HIV prevention of mother to child (PMTCT) programme. The sample interviewed included 139 HIV-positive antenatal women (mean gestational age 32 weeks; sexually transmitted diseases [STD] = 2.8, range 4-9 months) and 607 postnatal HIV-positive women, with either having an infant aged 1-10 weeks (30.8%), 11 weeks to 6 months (36.7%) or 7-12 months (32.5%) from Nkangala district, Mpumalanga province, South Africa. A large percentage of antenatal and postnatal women in this study initiated ARV prophylaxis for PMTCT or were on ARV (85.6% and 98%, respectively). Sixty-one per cent of antenatal and 85.9% of postnatal women reported complete adherence to the appropriate medication schedule in the 4 days preceding the interview or prior to delivery. In multivariate analysis, it was found that women with higher HIV status disclosure and less discrimination were better in maternal AZT adherence, women with higher male involvement were better in maternal and infant nevirapine adherence. Adherence to maternal and infant dual therapy prophylaxis was found to be less than optimal. Community factors (discrimination, HIV disclosure, male involvement) contribute to adherence to short-course ARV prophylaxis in this largely rural setting in South Africa. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.