The risk of exposed health care workers in 16 Italian hospitals becoming infected with hepatitis C virus was assessed through two serosurveys at a 1-year interval and at follow-up. Prevalence, which was 2.2%, was significantly associated with previous acute hepatitis, blood transfusions, housekeeping, and older age (> 46 years) but not with occupational risk factors. After 1 year, 2622 (87%) of the 3006 seronegative health care workers were retested, and 3 (0.1%), who did not acknowledge occupational or community risk factors, seroconverted. Additionally, 133 (97 needlesticks) out of 370 reported occupational exposures were to hepatitis C virus; one pricked nurse seroconverted (0.75%). Although the risk is not negligible, hepatitis C virus infection does not seem to be easily occupationally transmitted.