BACKGROUND Hepatitis B virus (HBV) reactivation is a fatal complication in patients who receive chemotherapy or immunosuppressive therapy. We examined the effect of preventive entecavir (ETV), a new nucleoside analogue on HBV reactivation during chemotherapy or immunosuppressive therapy. METHODS Between February 2007 and September 2009, sixteen nucleoside analogue treatment-naive patients with chronic HBV infection (HB surface antigen [HBsAg] positive) who required chemotherapy or immunosuppressive therapy were enrolled. Referring to some guidelines, the patients received preventive ETV to reduce incidence of HBV reactivation, and were closely monitored for HBV markers. RESULTS HBV reactivation did not occur in any of the 16 patients and the indispensable treatments for their underlying diseases could be continued. However, HBV relapsed after preventive ETV was discontinued in 2 patients. CONCLUSIONS This study suggests that ETV is a useful option for preventing HBV reactivation in patients with chronic HBV infection.