Hepatitis B virus (HBV) infection is an infectious disease that is specific to the liver, causing both acute and chronic hepatitis. This study determined the trend of HBV infection among blood donors in the Kpandai District Hospital from January 2014 to December 2018. Retrospective analysis of donor profiles for a period of 5 years was used to assess the distribution of seropositive cases in relation to age, sex, and trend. The data was collected using pre-designed questionnaire and managed using Microsoft Excel spread sheet 2013. The overall sero-prevalence of HBV was 8.2% (230/2802). The year to year analysis depicted significant trends in reduction of HBV infection among the study population at a rate of 13 percentage points above the mean from 2014 to 2015, and 4.3 percentage points below the mean from 2016 to 2018 across the period. The prevalence in males was 8.4% (225/2687) and that of the females was 4.4% (5/115) and the highest rate of infection was among those below 30 years 9.8% (163/1666). Although the general prevalence of HBV infection was high (8.2%), there was a significant trend reduction in rate of infection across the study period. This suggests that the public health interventional strategies put in place to manage the HBV infection in Kpandai District seem to be working.