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% [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.