Challenged by contrasting data on low immune responses in the elderly with a combined hepatitis A/B vaccine, a randomised, controlled study was conducted to assess the immunogenicity of three hepatitis A and B vaccination regimens (group 1: combined hepatitis A/B vaccine Twinrix [GSK]; group 2: co-administered hepatitis A vaccine, Havrix [GSK]+hepatitis B vaccine Engerix -B [GSK], group 3: co-administered hepatitis A vaccine, Vaqta [Sanofi-Pasteur MSD]+hepatitis B vaccine HB VAX PRO [Sanofi-Pasteur MSD]) and the effect of influencing factors in subjects >40 years. On completion of the full vaccination course, anti-HBs seroprotection (SP) rates were 92, 80 and 71% in groups 1, 2 and 3, respectively; anti-HAV seropositivity (S+) rates were 97, 99 and 99%, respectively. In group 1, anti-HBs SP rate was non-inferior as well as superior and anti-HAV S+ rate was non-inferior to that in groups 2 and 3. Anti-HBs response was most significantly influenced by the vaccine regimen, followed by age, gender and BMI (stepwise multiple regression analysis). BMI had the most significant influence on HAV response followed by age, gender and vaccine regimen. In conclusion, Twinrix induced superior hepatitis B SP rates and similar hepatitis A S+ rates compared to concomitant administration of monovalent vaccines in subjects aged >40 years.