Maternal co-infection with human immunodeficiency virus (HIV) has been implicated as a potentially important co-factor for enhanced vertical transmission of hepatitis C virus (HCV). In previous reports, however, methodological issues (notably small sample sizes) have limited accurate evaluation of the contribution of maternal co-infection with HIV on the risk of vertical transmission of HCV. A systematic review and subsequent meta-analysis of current published and unpublished reports was performed. Odds ratios (OR) and 95% CI for individual studies were calculated with maternal HIV serostatus as the exposure measure and HCV vertical transmission as the outcome measure. Overall summary estimates were then calculated using a random effects model that estimates a weighted average of OR from individual studies. In total, 2382 infants from 10 studies were included in an analysis of HCV-infected mothers (defined by anti-HCV+ antibody assays) with and without concomitant HIV infection. The risk estimate (OR) of HCV vertical transmission was 2.82 (95% CI: 1.78-4.45; P = 0.00001) from anti-HCV+/HIV+ co-infected mothers compared with anti-HCV+/HIV- mothers. In a subanalysis of 1327 infants born to viraemic (HCV RNA+) mothers, the risk estimate of HCV vertical transmission was 1.97 (95% CI: 1.04-3.74; P = 0.04) from HCV viraemic/HIV+ co-infected mothers compared with HCV viraemic/HIV- mothers. Results from this meta-analysis of observational studies suggest that the risk of HCV vertical transmission is higher in infants born to HIV co-infected mothers.