Hepatitis B is the most common and severe infection of the liver in the world including Ethiopia. This study was undertaken to assess the prevalence and possible association between risk factors and sero-positivity of Hepatitis B Virus surface antigen (HBsAg) among individuals visiting Woldia Health Center, northeast, Ethiopia. Hospital based cross-sectional study was conducted from November 2018 to February 2019. Blood samples were randomly collected from 415 individuals. Data on socio-demographic characteristics and potential risk factors were collected using structured questionnaire. HBsAg rapid kits were used to detect the presence of HBsAg using antibodies (if any) against HBV from serum samples of the studied subjects. Chi-square test was used for assessing the association between socio-demographic variables and HBV status. Logistic regression analysis was done to determine the strength of association between risk factors and HBV infection. Prevalence of hepatitis B was 3.37%. Amongst the potential risk factors analyzed in univariate logistic regression, sex (COR= 3.759, CI: 1.274-11.087, P= 0.016), smoking (COR= 6.517, CI: 1.286-33.035, P= 0.024), previous experience of liver disease (COR= 11.879, CI: 2.822-50.010, P= 0.001), previous experience of TB or cancer (COR=8.187, CI: 1.568-42.740, P= 0.013), having multiple sexual partners (COR= 6.614, CI: 2.032-21.525, P= 0.002), and abortion (COR= 10.082, CI: 1.797-56.574, P= 0.009) were significantly associated with hepatitis B infection. Nevertheless, only the variable, previous experience of liver disease, remained as a statistical significant explanatory risk factor in multivariate logistic regression (AOR= 30.69, P= 0.013) analysis. This study found an intermediate endemicity (3.37 %) of HBV infection and it was very small, but this needs to be confirmed by other studies at community level. Thus, screening of individuals for HBV infections and administration of health information about the risk factors, the mode of transmissions and prevention is recommended.