A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB (®) (Heber Biotec S.A., Havana, Cuba), Euvax-B (®) (LG Chemical Ltd., Seoul, Korea), Hepavax-Gene (®) (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B (®) (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 - 2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B (®) , Hepavax-Gene (®) , Euvax-B (®) , and Heberbiovac-HB (®) vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB (®) vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB (®) showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB (®) . [WHO primary Registry Number: RPCEC00000075].