Hepatitis C virus (HCV) is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). HCV infection status among HCWs and occupational blood exposure accidents were monitored to assess the risk of HCV infection among 403 HCWs from a single institution between 1999 and 2009. Additionally, HCV-related malignancies were evaluated in the HCV-positive HCWs. HCV infection was detected in 3% of the subjects at the first survey. The HCWs that initially tested negative for HCV remained negative during the 10 years of the survey. Of note, a statistically significant decrease was observed in the number of HCWs that experienced occupational blood exposure accidents, from 116 in 1999 to 72 in 2009 (p=0.0002). One HCV-infected HCW developed B-cell non-Hodgkin lymphoma (NHL) of the liver. The heavy chain gene combinations detected in the DNA from the NHL tissue were of the type usually found in HCV-associated lymphomas, supporting the role of HCV infection in the lymphomagenesis of this patient. The set of universal precautions recommended by the US Center for Disease Control and Prevention aided in the prevention of HCV transmission from patients to HCWs, as all 390 HCV-negative HCWs remained negative for the duration of the survey. Consequently, these recommendations also serve to prevent the development of HCV-associated malignancies such as hepatocellular carcinoma or B-cell NHL.