Blood transfusions carry risks of untoward reactions, including the transmission of infections, such as hepatitis B. But about 50% of these blood donors and blood recipients have had natural exposure to hepatitis B virus (HBV) and therefore perceived to have natural immunity against HBV. In view of this, the need for hepatitis B surface antigen (HBsAg) testing of blood donors before donation has often been over looked. This has resulted in about 50% of blood donors not going through screening for HBsAg in sub-Saharan Africa. This study examined the potential risk of acquiring transfusion-transmitted hepatitis B infection in the Cape Coast, Ghana. A total of three hundred and thirty nine potential blood donors were screened for HBsAg using a rapid test (1–2 IU ml-1sensitivity) (Determine, Abbott Laboratories). A total of 33 of the subjects were reactive, representing a prevalence of 9.7%. Prevalence among males and females were 10.5% and 8.9% respectively. Subjects who were between the ages of 22 and 25 years recorded the highest reactive cases of 48%. Prevalence of 7.7%, 20.6% and 3.7% were recorded for students, Artisans and Teachers respectively. The prevalence of prospective donors who were reactive to HBsAg was high and consistent with other similar studies reported in literature. Hence, screening for HBsAg should be performed on prospective blood donors before donation in the Cape Coast metropolis in Ghana and all other places with high prevalence.