The purpose of this study was to measure the association between maternal HIV infection and infant mortality in Ghana. Using a censored synthetic cohort life table based on the birth history of 3,639 childbirths during 1999–2003 obtained from the interviews of a nationally representative sample of 5,691 women age 15–49 in 6,251 households in the 2003 Ghana Demographic and Health Survey. The survey collected demographic, socioeconomic, and health data of the respondents as well as obtained voluntary counseling test for HIV infection from all eligible women. The effects of maternal HIV status and other factors on infant mortality were estimated using multivariate survival regression analysis and the results are presented as Hazard Ratios (HR) with 95% confident interval (95% CI). Children born to HIV infected mothers were three times as likely to die during infancy as those born to uninfected mothers (HR=3.01; 95% CI: 1.64, 5.50). Controlling for other factors affecting infant mortality further sharpens this relationship (HR=3.51; 95% CI: 1.87, 6.61). Not receiving antenatal care, low birth weight, and living in households that use high pollution cooking fuels were associated with a higher risk of infant mortality. Maternal HIV status is a strong predictor of infant mortality in Ghana, independent of several other factors. The results of this study suggest that HIV/AIDS epidemic has had great impact on child well-being and child survival. This impact tends to increase as the HIV/AIDS epidemic matures and infection in adults increases.