The interchangeability of virosomal (Epaxal) and aluminum-adsorbed (Havrix 1440) hepatitis A virus (HAV) vaccines was studied in 111 healthy adults who were vaccinated in a randomized, single-blind, crossover clinical trial. Anti-HAV antibody titers were measured at days 0 (first dose), 14, and 28, and months 3, 6, 12 (second dose), 13, 24, 36, 48, 60 and 72. Most subjects (>95%) had sero-converted 14 days after the first dose of either vaccine. The second dose with either vaccine induced a high antibody response in all vaccines, irrespective of the type of vaccine administered as the first dose. Although both vaccines were well tolerated, the incidence of local adverse events (in particular pain) was significantly lower in subjects receiving the virosomal vaccine. Six-year follow-up data did not reveal any significant differences between the vaccination groups.