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Objectives: To improve uptake in a program to prevent mother-to-child HIV transmission and describe lessons relevant for prevention of mother-to-child transmission programs in resource-poor settings., Methods: Implementation of a pilot project that evaluates approaches to increase program uptake at health facility level at New Nyanza Provincial General Hospital, a public hospital in western Kenya, an area with high HIV prevalence. Client flow was revised to integrate counseling, HIV testing, and dispensing of single-dose nevirapine into routine antenatal services. The number of facilities providing PMCT services was expanded to increase district-wide coverage. Main outcome measures were uptake of counseling, HIV testing, nevirapine, and estimated program impact., Results: Uptake of counseling and testing improved from 55 to 68% (P < 0.001), nevirapine uptake from 57% to 70% (P < 0.001), and estimated program impact from 15% to 23% (P = 0.03). Aggregate reports compare well with computer-entered data., Conclusion: Addressing institutional factors can improve uptake, but expected program impact remains low for several reasons, including relatively low efficacy of the intervention and missed opportunities in the labor room.