This study aimed to evaluate loss of protective anti-hepatitis B (HBs) titers and seroconversion to hepatitis B vaccine (HBV) during chemotherapy in children with acute lymphoblastic leukemia (ALL). Anti-HBs titers were done at diagnosis. Patients were divided into two groups. Group I (protective titers >10mIU/ml) received single double dose of HBV as booster. Titers were repeated at three time points: end of phase 1b, beginning of re-induction, and start of maintenance chemotherapy. Group II (nonprotective titers <10mIU/L) received hepatitis B immunoglobulin (HBIG), prior to start of chemotherapy, followed by three double doses of HBV as booster. Titers were repeated at two time points: prior to first dose, and 4weeks after third dose of vaccine. Total 125 patients were included: 88 in group I; 37 in group II. Among group I patients, 98.7%, 90%, and 84% retained protective titers at the three points, respectively. Subgroup analysis showed that those with initial titers greater than 100mIU/L retained protective titers better than those with titers between 11 and 100mIU/L (p = .0001). Among group II patients, 62% and 64% attained protective titers at the two points, respectively. HBV boosters helped maintain protective titers during intensive ALL chemotherapy in immunized children having titers more than 10mIU/L, and more so if titer was more than 100mIU/L. Therefore, we propose that cut off for protective anti-HBs titers be changed to greater than or equal to 100mIU/L. Titers between 11 and 100mIU/L may require combined active and passive immunization. Around one-third of group II patients who fail to attain protective titers may need frequent doses of HBIG.