Research Question: To date, no studies on risk factors for hepatitis C virus (HCV) transmission to healthcare workers have been identified. The objective of this study is to determine the risk factors for accidental HCV transmission to healthcare workers following a blood-exposure incident (BEI). Methods: The study was based on a European case-control survey. Cases were healthcare workers not infected with HCV who experienced a BSE between January 1, 1993, and December 31, 2002, with an HCV-infected source patient and who seroconverted to hepatitis C virus. Controls were HCV-uninfected healthcare workers who contracted an AES from an HCV-infected source patient but did not seroconvert to HCV within 6 months of the incident. Cases and controls were matched by healthcare facility and by the period of AES occurrence. Results: Sixty cases and 204 controls were included. All cases were infected following a percutaneous accident. Of the 60 cases for which data were available, 37 were exposed to viremic source patients. In the multivariate analysis, the risk factors for accidental HCV transmission to healthcare workers were: intravenous and intra-arterial procedures (Odds Ratio [OR] = 100.1; 95% confidence interval [CI] = 7.3–1,365.7), deep puncture (OR = 155.2; 95% CI = 7.1–3,417.2), and gender (male vs. female healthcare worker: OR = 3.1; 95% CI = 1.0–10.0). The source patient’s viral load was not included in the multivariate model due to missing data. In the unpaired univariate analysis, the risk of HCV transmission was 11 times higher among healthcare workers exposed to source patients with a viral load > 6 log10 copies/mL (95% CI = 1.1–114.1) compared to those exposed to patients with a viral load < 4 log10 copies/mL. Conclusion: The risk of hepatitis C virus transmission following a percutaneous injury is associated with the procedure being performed, the depth of the injury, and the viral load in the source patient. The results of this study will enable us to develop appropriate recommendations regarding follow-up after a percutaneous injury.