Objectives: To avoid further transmission of hepatitis B virus (HBV) infection, blood is tested for hepatitis B surface antigen (HBsAg) before transfusion. However, post-transfusion hepatitis B has been detected in clinics after transfusion of HBsAg-negative blood. The study presented here was undertaken to assess if HBsAg-negative blood is free from HBV or not. Methods: Sera were collected from 398 blood donors who were negative for HBsAg. Out of 398 blood samples, antibody to hepatitis B core antigen (ant-HBc) was detected in 82 sera samples. HBV DNA was evaluated in HBsAg-negative, anti-HBc-positive sera. HBsAg, hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), and anti-HBc in the sera were measured by an enzyme-linked immunosorbent assay (ELISA). HBV DNA was quantified by a real time polymerase chain reaction (PCR). Results: Out of 82 HBsAgnegative, anti-HBc-positive sera samples, HBV DNA were detected in the sera of 7 voluntary blood donors. Out of these 7 subjects, all were negative for HBeAg. The levels of ALT were more than 30 IU/L in 6 of 7 HBVDNApositive subjects and it was above upper limit of normal (>42 IU/ml) in one subject. Conclusions: The present recommendation about blood transfusion of HBsAg-negative blood system is not capable of blocking HBV transmission to blood recipients. Although advanced countries have adopted nucleic acid testing (NAT) for preventing HBV transmission, developing countries may apply anti-HBc testing and ALT estimation before blood transmission. ( J CLIN EXP HEPATOL 2016;6:115-118) I mportant insights have been developed about epidemiology, virology, molecular biology, immunology, and pathogenesis, mode of transmission, prevention and treatment of hepatitis B virus (HBV) during last three decades. 1 Although satisfactory treatment modalities are yet to be surfaced, 2 significant developments have been achieved regarding prevention of HBV infection. 3,4 Potent vaccines against HBV are widely used as part of expanded program of immunization around the world. Public health measures have been accentuated to ensure HBV-free safe childbirth. Also, attention has been given for safe transfusion of blood. Taken together, it is now clear that HBV prevention is an achievable goal. In fact, new HBV infection has been a rare entity in most developed and advanced countries with improved health care delivery system. However, the beneficial effects of different HBV prevention programs have not been properly implemented in developing and resource-constrained countries of the world as several millions of new HBV infection emerges every year in developing countries of the world.Bangladesh, a developing country of South-East Asia, has a population of 160 million. HBV is the most common cause of chronic liver diseases including cirrhosis of liver, hepatic failure, and hepatocellular carcinoma. The risk of acquiring new HBV infection has been reduced in Bangladesh with the introduction of hepatitis B surface antigen (HBsAg) screening in blood donors. However, with the advent of ...