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Background: HBV infection is a significant health problem in Egypt which is categorized as an HB virus intermediate endemic area, with HB carrier rate ranging from 2%-7%. HBV infection is the 10th leading cause of death and HBV related hepatocellular carcinoma is the 5th most frequent cancer worldwide. Aims of the study: The present study aims to investigate the most important risk factors for transmission of HBV and HCV in urban and rural areas in Qena Governorate, Egypt. Patients and Methods: A matched case control study was conducted. The study included 600 patients, 100 HBV cases and 500 controls, aged above 20 years and below 70 years. Direct interview was done with each participant separately for filling the questionnaire during the period from January 2013 to January 2014. The collected data were reviewed, entered and statistically analyzed using SPSS version 19. Results: The mean age of cases and controls were 38.83 (± 12.62) and 44.26 (± 11.68) years respectively. Multivariate analysis shows that odds ratio of HBV infection is significantly higher among cases with some risk factors: injection by reused needle, sharing razors with others, dental procedures or oral surgery, blood transfusion and intravenous infusion and/or injection. Conclusion and Recommendations: The common risk factors exposures of hepatitis B infection included blood transfusion, dealing with patient blood, hospital admission, surgery, accidental stick with a blood contaminated needle, intravenous catheterization and dental procedures. There are statistically significant differences between HBV cases and their controls in the majority of these risk factors. The presence of these risk factors emphasizes the need for increasing the uptake of HB vaccine. Health care providers, health educators, and other community-based organizations must play an active role in counseling high-risk people