CONTEXT: In Israel, the mean annual incidence of hepatitis A disease was 50.4 per 100 000 during 1993-1998. A 2-dose universal hepatitis A immunization program aimed at children aged 18 and 24 months (without a catch-up campaign) was started in 1999. OBJECTIVE: To observe the impact of toddlers-only universal vaccination on hepatitis A virus disease in Israel. DESIGN AND SETTING: Ongoing passive national surveillance of hepatitis A cases in Israel has been conducted since 1993 by the Ministry of Health. An active surveillance program in the Jerusalem district in 1999-2003 provided validation for the passive program. MAIN OUTCOME MEASURE: Incidence of reported hepatitis A disease, 1993-2004. RESULTS: Overall vaccine coverage in Israel in 2001-2002 was 90% for the first dose and 85% for the second dose. A decline in disease rates was observed before 1999 among the Jewish but not the non-Jewish population. After initiation of the program, a sharp decrease in disease rates was observed in both populations. The annual incidence of 2.2 to 2.5 per 100 000 during 2002-2004 represents a 95% or greater reduction for each year with respect to the mean incidence during 1993-1998 (P<.001). For children aged 1 through 4 years, a 98.2% reduction in disease was observed in 2002-2004, compared with the prevaccination period (P<.001). However, a sharp decline was also observed in all other age groups (84.3% [<1 year], 96.5% [5-9 years], 95.2% [10-14 years], 91.3% [15-44 years], 90.6% [45-64 years], and 77.3% [>or=65 years]). Among the Jewish population in the Jerusalem district, in whom the active surveillance program was successfully conducted, a more than 90% reduction of disease was demonstrated. Of the 433 cases reported nationwide in 2002-2004 in whom vaccination status could be ascertained, 424 (97.9%) received no vaccine and none received 2 doses. CONCLUSION: This universal toddlers-only immunization program in Israel demonstrated not only high effectiveness of hepatitis A vaccination but also marked herd protection, challenging the need for catch-up hepatitis A vaccination programs.