NAT screening for HBV has been introduced when multiplex technology was available only in countries where the endemic of HBV was on medium/high level and where the screening with other serological tests, like anti-HBc, was impossible without impair self-sufficiency in blood procurement. The first goal of NAT testing introduction in blood screening was to increase the sensibility of screening tests in order to impair transfusion of blood units from subjects in initial acute phase of infection with no other serological markers (window period shortage). But after HBV NAT implementation the great majority of NAT HBV positive/HBsAg negative subjects are represented by repeat donors with other serological markers of previous contact with HBV (anti-HBc and anti-HBs), with low viral load and totally silent from the clinical point of view. In the 2001–2008 period 7,436,996 blood units were tested, in Italy, for HBV DNA and 383 resulted positive: 20 of them (1:372.000) were subjects in acute phase of the infection and seroconverted, 363 (1:20.000) were OBI. Similar pictures are observed in other Mediterranean and East Europe Countries. These data could induce all mathematical models, finalized to calculate the residual risk, to consider HBV as the main infectious risk in transfusion field. But we can observe, where HBV DNA blood screening is in progress since some years, a downward trend of OBI blood donors: in Italy 61.9×106 subjects have been observed in 2005 and 42.2×106 in 2008 (p < 0.05). On the contrary, acute cases are stable. In addition, there are some doubts about the actual capacity of OBI subjects to infect the recipient: some experiences showed that HBV DNA of OBI subjects is less efficient in transmitting the infection than DNA of acute phase subjects.Nevertheless, HBV transfusion transmitted infections from blood donors with low viral load are still reported. In conclusion blood screening with both HBsAg and HBV DNA test is, at the moment, the best way for HBV safe transfusion; in the meantime it limits donors deferral only to those who are really at risk of transmitting a HBV infection. In the future the occurrence of blood donors with OBI will decrease due to progressive deferral of these subjects and to the vaccination campaigns against HBV in progress in countries at medium/high level of HBV endemic.