We have investigated two cases of acute hepatitis C that occurred in patients who underwent digestive endoscopy and contrast-enhanced computed tomography (CT) scanning at two different centers. Investigations to identify the sources of infection included an on-site review of diagnostic procedures, interview of the involved healthcare staff, serological testing of the patients who underwent the procedures before and after the index cases and a molecular analysis of viral isolates from the patients and from potential viremic sources. In both cases, the epidemiological investigation identified a chronic hepatitis C virus (HCV) carrier who had been subjected to CT-scanning immediately before the index patient. Genetic distance and molecular phylogenetic analyzes of HCV sequences showed a close relationship between the isolates from these carriers and those from the acute-hepatitis patients, strongly suggesting that patient-to-patient transmission had occurred during CT. This is the first report describing two well documented cases of HCV nosocomial patient-to-patient transmission during contrast-enhanced CT scanning.