Scale-up of vertical HIV transmission prevention has been too slow in sub-Saharan Africa. We describe approaches, challenges, and results obtained in Kinshasa. Staff members of 21 clinics managed by public servants or non-governmental organizations were trained in improved basic antenatal care (ANC) including nevirapine (NVP)-based HIV transmission prevention. Program initiation was supported on-site logistically and technically. Aggregate implementation data were collected and used for program monitoring. Contextual information was obtained through a survey. Among 45,262 women seeking ANC from June 2003 through July 2005, 90% accepted testing; 792 (1.9%) had HIV of whom 599 (76%) returned for their result. Among 414 HIV+ women who delivered in participating maternities, NVP coverage was 79%; 92% of newborns received NVP. Differences were noted by clinic management in program implementation and HIV prevalence (1.2 to 3.0%). Initiating vertical HIV transmission prevention embedded in improved antenatal services in a fragile, fragmented, severely resource-deprived health care system was possible and improved over time. Scope and quality of service coverage should further increase; strategies to decrease loss to follow-up of HIV+ women should be identified to improve program effectiveness. The observed differences in HIV prevalence highlight the importance of selecting representative sentinel surveillance centers.