Aim: Hepatitis C virus (HCV) is a major cause of cirrhosis, liver cancer, and mortality worldwide. Egypt has the highest burden of Hepatitis C in the world. HCV prevalence is directly related to the prevalence of persons who routinely share injection equipment and to the prevalence of unsafe parenteral practices in healthcare settings. The study aimed to identify risk factors associated with HCV infection among adults. Material and Methods: This case control study nested from a household survey that was conducted to screen for hepatitis B virus and hepatitis C virus was conducted in Damietta Governorate, Egypt. One hundred-fifty cases and controls were randomly selected from those showed positive HCV (278) and 300 controls were randomly selected from those showed negative HCV (2699). Results: Participants were aged between 20 and 67 years (mean 42.0 +10.6 years). The study revealed a significant difference between case and control group regarding age, residence, education level and marital status (P = 0.001). Case-patients were more likely than controls to have exposure to dental procedure, previous stitches, surgical operation schistosomiasis injection treatment, blood transfusion and intravenous(IV) fluid intake were significantly associated with HCV infection (P < 0.05). Also, unsafe community practices (cupping, acupuncture, shared shaving razor, traditional cauterization, needle or sharp stick and tattooing) were significantly different between HCV-infected patients and controls (P < 0.01). In multivariable analysis, marital status and rural residence and history of stitches, intravenous fluid, dental procedure, renal dialysis, sharing shaving razor, acupuncture, needle or sharp stick and cupping were associated with higher odds of having HCV. Discussion: The results of this study showed that exposure to unsafe medical procedures and social practices were risk factors for HCV infection. Promotion of infection control programs in healthcare settings and health education campaigns to increase the awareness and empowerment of the community are strongly recommended.