To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as >or=2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.