Background: Worldwide, prevalence of anti-HCV positivity in health care workers (HCWs) ranges from 0% to 9.7%. The current study was conducted to calculate prevalence of HCV infection, frequency and characteristics of blood and body fluid (BBF) exposure among HCW at the Alexandria University Hospitals. Methods: Hospital-based cross-sectional approach was adopted. At the Hospitals, 62.2% of available nurses and paramedical personnel voluntarily participated (n = 499), and were interviewed, screened for HCV antibodies. Quantitative estimation of HCV-RNA was done to seropositive cases. Results: Prevalence of anti-HCV antibodies and HCV infection was 8.6%, and 4.4% respectively. The frequency of BBF exposures was 66.7%. Blood/blood products were mainly involved (92.1%). More than half of exposed HCWs reported not wearing personal protective devices. Anatomical site of exposure was mainly right hand palm (36.2%). Regarding needle-stick injuries, two thirds of injured HCWs were the original user of sharp item which was contaminated in 79.7% of injuries. In 70.2% of injuries, disposable syringes were involved and occurred during item disposal. About 61% of injuries were superficial. Conclusion: Prevalence of HCV infection among HCWs is similar to that among general population in the country. Nurses and housekeepers are frequently exposed to BBF. Adherence to infection control measures according to the National Guidelines is crucial to reduce HCV transmission.