Our objective was to develop a prediction model for hepatitis C virus (HCV) infection perinatal transmission to improve triage for neonatal follow-up. This was a secondary analysis of HCV antibody-positive participants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network multicenter observational study of HCV infection in pregnancy. Among 432 participants, the perinatal transmission rate was 6.0% (95% CI, 4.0-8.7%). The prediction model was developed and included two factors: maternal HCV RNA titer greater than 10 6 international units/mL and having had any antepartum bleeding. Using this model, the area under the curve for perinatal transmission was 0.76 (95% CI, 0.67-0.86). Probabilities of perinatal transmission of HCV infection ranged from 1.5% (a pregnant individual with HCV RNA 10 6 international units/mL or less and no antepartum bleeding) to 28.5% (a pregnant individual with an HCV RNA titer greater than 10 6 international units/mL and antepartum bleeding). Our results provide data to aid in clinical counseling of pregnant individuals with positive HCV antibodies. Additional research is needed to externally validate this prediction model.