To characterize longitudinal hepatic toxicity of antiretroviral therapy in HIV-infected women with and without hepatitis C virus (HCV) infection, we measured alanine and aspartate aminotransferase values among women initiating highly active antiretroviral therapy (HAART). For 312 HIV/HCV coinfected women who received HAART for a mean of 1.8 years, the prevalence of elevated aminotransferase levels >3 times and >5 times the upper limit of normal (ULN) was low (<12% and <4%, respectively), and the prevalence of elevated aminotransferase levels declined over time. When we analyzed trends in aminotransferase levels according to type of HAART received among HCV-infected and uninfected women, we found that mean aminotransferase levels declined among 539 women receiving therapy with protease inhibitors (decreases of 5.34%-4.23% of the ULN per year; P values for trend of.007-.06), but mean values among 128 women receiving therapy with nonnucleoside reverse-transcriptase inhibitors remained stable (from decreases of 1.65% to increases of 7.57% of the ULN per year; P values of.19-.71). Our findings lend support to assertions that antiretroviral therapy is safe for women with HCV infection.