Background: in spite of teh progress in teh prevention of transfusion transmitted infections over the last few years, transmission of hepatitis B virus (HBV) infection through transfusion of hepatitis B surface antigen (HBsAg) negative blood has been documented. Objective: to study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in Egypt as a screening assay for HBV in addition to HBsAg. Methods: in a cross sectional study, a total of 3043 blood donors were screened in 2009 for teh following viral markers; hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and human immunodeficiency virus I/II (anti-HIV I/II). Nine hundred and four samples negative for HBsAg (323 samples with elevated ALT level and 581 with normal ALT level) were tested for the presence of anti-HBc. Results: one hundred and sixty two samples (17.92%) were reactive for anti-HBc. The present study showed 20.12* and 16.7% anti-HBc positivity for samples with elevated and noraml ALT level respectively.  Conclusion: anti-HBc should be tested routinely in blood donor volunteers. Rejection of anti-HBc positive units will be beneficial in decreasing the risk of HBV transmission with its potential consequences.