This study aimed to describe current epidemiological and clinical characteristics, medical follow-up and outcome in the real practice of acute hepatitis C (AHC) patients. AHC cases were retrospectively identified through the French Hepatology Reference Centres Surveillance system and additional data were collected. Sixty-one patients with AHC were identified (sex ratio: M/F 1.7/1; mean age 39 years). Forty-four (72%) had documented seroconversion within a 6-month period. Main reported risk exposures were intravenous or nasal drug use (35%), invasive medical procedures (25%) and sexual contact with a HCV-positive partner (20%). Spontaneous clearance of HCV RNA was observed in seven out of 16 patients followed without therapy. This study confirms the major role of drug use in HCV transmission and highlights the role of invasive medical procedures and occupational exposure.