The prevalence of HBV infection among male Saudi blood donors in the northwest region of Saudi Arabia is high compared to that reported from the central capital area (Riyadh). Public health education programs on HBV infection, adult hepatitis B immunization programs, and raising socioeconomic standards should be initiated in order to target the high-risk groups found in this study. Furthermore, a community-based study is recommended to investigate HBV infection in the northwest region of Saudi Arabia.