The World Health Organization recommends a single-dose nevirapine (NVP) regimen for prevention of mother-to-child transmission (PMTCT) of HIV in settings without the capacity to deliver more complex regimens, but the population-level impact of this intervention has rarely been assessed.A decision analysis model was developed, parameterized, and applied using local epidemiologic and demographic data to estimate vertical transmission of HIV and the impact of the PMTCT program in Zimbabwe up to 2005.Between 1980 and 2005, of approximately 10 million children born in Zimbabwe, a cumulative 504,000 (range: 362,000 to 665,000) were vertically infected with HIV; 59% of these infections occurred in nonurban areas. Mother-to-child transmission (MTCT) of HIV decreased from 8.2% (range: 6.0% to 10.7%) in 2000 to 6.2% (range: 4.9% to 8.9%) in 2005, predominantly attributable to declining maternal HIV prevalence rather than to the PMTCT program. Between 2002 and 2005, the single-dose NVP PMTCT program may have averted 4600 (range: 3900 to 7800) infections. In 2005, 32% (range: 26% to 44%) and 4.0% (range: 2.7% to 6.2%) of infections were attributable to breast-feeding and maternal seroconversion, respectively, and the PMTCT program reduced infant infections by 8.8% (range: 5.5% to 12.1%). Twice as many infections could have been averted had a more efficacious but logistically more complex NVP + zidovudine regimen been implemented with similar coverage (50%) and acceptance (42%).The decline in MTCT from 2000 to 2005 is attributable more to the concurrent decrease in HIV prevalence in pregnant women than to PMTCT at the current level of rollout. To improve the impact of PMTCT, program coverage and acceptance must be increased, especially in rural areas, and local infrastructure must then be strengthened so that single-dose NVP can be replaced with a more efficacious regimen.