© 2005 by the Infectious Diseases Society of America. All rights reserved. Background. Risk factors for mother-to-child transmission of hepatitis C virus (HCV) are poorly quantified Methods. We conducted a European multicenter prospective study of HCV-infected pregnant women and their infants. Children with ≥2 positive HCV RNA polymerase chain reaction test results and/or anti-HCV antibodies after 18 months of age were considered to be infected. Results. The overall HCV vertical transmission rate was 6.2% (95% confidenc interval [CI], 5.0%–7.5%; 91/1479). Girls were twice as likely to be infected as boys (adjusted odds ratio [OR], 2.07 [95% CI, 1.23–3.48];). P =.006 There was no protective effect of elective cesarean section (CS) delivery on HCV vertical transmission (adjusted OR, 1.46 [95% CI, 0.86–2.48]; P =.16). HCV/human immunodeficienc virus-coinfected women more frequently transmitted HCV than did women with HCV infection only, although the difference was not statistically significan (adjusted OR, 1.82 [95% CI, 0.94–3.52]; P =.08). Maternal history of injection drug use, prematurity, and breast-feeding were not significantl associated with transmission. Transmission occurred more frequently from viremic women, but it also occurred from a few nonviremic women. Conclusions. Our results strongly suggest that women should neither be offered an elective CS nor be discouraged from breast-feeding on the basis of HCV infection alone. The sex association is an intriguing findin that probably reflect biological differences in susceptibility or response to infection.