OBJECTIVE: To assess the relationship between mode of delivery and subsequent maternal HIV-1 disease progression. DESIGN AND METHODS: Changes in CD4+ lymphocyte percentage (CD4%) and plasma HIV-1 RNA concentration (HIV RNA), and time to progression to AIDS or death among HIV-1-infected women were compared according to mode of delivery [cesarean section before labor and ruptured membranes (SCS), cesarean section after labor and/or after ruptured membranes (NSCS), and vaginal delivery]. Generalized estimating equations were used to compare changes in adjusted mean CD4% and HIV RNA counts by mode of delivery. Cox proportional hazard models were used to assess differences in time to AIDS or death. RESULTS: In adjusted analyses, there were no clinically important differences in HIV-1 disease progression according to mode of delivery (SCS, n = 183; NSCS, n = 221; vaginal, n = 1087), as assessed by changes in CD4% and HIV RNA during the 18 months following delivery, and by progression to AIDS or death during a mean postpartum follow-up of 2.66 years. CONCLUSIONS: The present results suggest that, among HIV-1-infected women in North America, mode of delivery is not associated with subsequent HIV-1 disease progression.