The aim of this study was to determine changes in the epidemiology of hepatitis A virus (HAV) infection in the Basque Country, Spain, and to evaluate their implications for vaccination strategies. A total of 1356 persons were enrolled in a study of the prevalence of anti-HAV in 2004 and compared with two previous studies (1986-1987 and 1992). The selection method and the characteristics of the population were similar in the three studies. A marked decline in the seroprevalence in all age groups (P<0.001) and in the incidence of cases/100,000 inhabitants (from 38.0 in 1986-1988 to 2.9 in 2002-2004) were observed. The mean age of patients with hepatitis A increased from 17.7 years in 1986-1992 to 21.2 years in 1993-1998 and 25.3 years in 1999-2004 (P<0.001). Between 1997 and 2004, 20% of patients were hospitalized. The changes observed have occurred rapidly causing a change in the epidemiological pattern from middle-high endemicity (1986) to low endemicity (2004).