The objective of the study was to assess the effectiveness of federal funds in preventing perinatal human immunodeficiency virus (HIV) transmission in the United States. We used surveillance data from 1999 and 2001 in 6 funded areas to estimate the proportion of HIV-infected women prescribed perinatal prophylaxis and whose infants were HIV infected. We compared outcomes with 5 unfunded areas in which surveillance data were available. The proportion of funded-area women prescribed prophylaxis increased from 80.1% to 85.9% (P < .01), compared with a decline in unfunded areas from 95.1% to 86.7% (P < .01); the difference in trends between groups was P < .01. The perinatal HIV transmission rate for funded areas declined from 6.5% (105 cases) in 1999 to 3.4% (46 cases) in 2001 (P < .01), compared with a decline in unfunded areas from 4.3% (19 cases) to 3.4% (13 cases) (P = .59); the difference in trends between groups was P = .24). The number of perinatal HIV infections in the funded areas decreased by 56%, achieving the Centers for Disease Control and Prevention's goal of a 50% reduction in incidence by 2005.