In Western countries, the risk of hepatitis C virus (HCV) transmission through blood transfusion has been very low since the mid-1990s. Knowledge of current modes of transmission needs to be updated. However, the study of risk factors has so far relied primarily on prevalent cases of HCV infection. In this article, we describe the main case-control studies in terms of methods and key findings that have contributed to our understanding of transmission modes. We also report the results of a recent incident case-control study conducted in France, which confirms the major role of intravenous drug use in the current dynamics of HCV infection and shows that transmission linked to invasive medical procedures remained a potential source of HCV infections between 1995 and 2001.