In this prospective study, our aim was to test the effect of simultaneous administration of preS2 and S containing recombinant hepatitis B vaccine (S2SRHB) with tetanus toxoid (TT) to the individuals who did not respond after three doses of hepatitis B vaccine previously. There were three groups (healthy individuals, pregnant women, hemodialysis patients), each was divided into two subgroups as groups A and B. Group A received S2SRHB+TT and group B received only S2SRHB. We found that in groups receiving both vaccines, both seroconversion rate and antibody titer level were significantly higher (P<0.05). In conclusion, simultaneous administration of S2SRHB+TT is more effective than administration of S2SRHB alone.