OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2% (95% CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.