Tattoos and piercings are increasing, especially among youths, but the risk of hepatitis C virus (HCV) infection from these practices has not been adequately assessed and there are conflicting findings in the literature. We evaluated the risk of HCV infection from tattooing and piercing using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies that specified the venue of tattooing and/or piercing showed no definitive evidence for an increased risk of HCV infection when tattoos and piercings were received in professional parlors. However, the risk of HCV infection is significant, especially among high-risk groups (adjusted odds ratio, 2.0-3.6), when tattoos are applied in prison settings or by friends. Prevention interventions are needed to avoid the transmission of hepatitis C from tattooing and piercing in prisons, homes, and other potentially nonsterile settings. Youths also should be educated on the need to have tattoos and piercings performed under sterile conditions to avoid HCV infection.