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This prospective multicenter study evaluated separately the significance of maternal injection drug use (IDU) and human immunodeficiency virus type 1 (HIV-1) coinfection in vertical transmission of hepatitis C virus (HCV). In all, 1372 consecutive, unselected HCV antibody-positive mothers and their infants were studied. Maternal HIV-1 coinfection (crude odds ratios [OR], 1.41; 95% confidence interval [CI], 1.16–1.66; P = .007) and IDU (OR, 1.58; 95% CI, 1.37–1.78; P < .00001) were linked to mother-to-child HCV transmission in unadjusted analysis when all anti-HCV-positive mothers were evaluated. When only HCV RNA-positivemothers were evaluated, maternal IDU, but not maternal HIV-1 coinfection, was significantly associated with mother-to-child HCV transmission. Multivariable analysis confirmed the link between maternal IDU and HCV transmission (adjusted OR [AOR], 1.51; 95% CI, 1.19–1.92; P …