Background:To assess the postnatal transmission (PT) risk of HIV-1 after a maternal short-course zidovudine regimen in a breastfeeding population.Methods:Data were pooled from two trials: ANRS 049a DITRAME (Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina-Faso) and RETROCI (Abidjan). Consenting HIV-1 seropositive women were randomized at 36–38 weeks’ gestation between September 1995 and February 1998, to receive oral zidovudine or placebo: one tablet twice daily until delivery, and in DITRAME only, for 7 more days. A PT case was infection in a child with a negative HIV-1 PCR at age ⩾ 30 days who later became infected as defined by a positive HIV-1 PCR, or if aged ⩾ 15 months, a positive HIV serology. Cumulative risks (CR) of PT were computed using a competing risk approach with weaning as a competing event.Findings:At age 24 months, CR for PT were similar in the zidovudine (9.8%, n = 254) and placebo groups (9.1%, n = 225). In a multivariate model of PT risk factors, the treatment effect was not significant, maternal CD4 cell count < 500 × 106/l at entry tripled the hazard compared to women with CD4 cell counts ⩾ 500 × 106/l [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.31–7.49] as well as an increased maternal plasma viral load at entry (HR, 2.65 for 1 log10increase; CI, 1.75–4.00).Interpretation:PT occurred at a similar rate between arms and therefore reduced the long-term overall efficacy of this peripartum zidovudine regimen at age 24 months. The higher risk of PT among women with low CD4 cell count emphasizes the importance of identifying interventions to prevent PT for these women.