Our objective was to assess trends in the prevalence of hepatitis B virus (HBV) infection in the United States after widespread hepatitis B vaccination.The prevalence of HBV infection and immunity was determined in a representative sample of the US population for the periods 1999-2006 and 1988-1994. National Health and Nutrition Examination Surveys participants 6 years of age were tested for antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B surface antigen (anti-HBs). Prevalence estimates were weighted and age-adjusted.During the period 1999-2006, age-adjusted prevalences of anti-HBc (4.7%) and HBsAg (0.27%) were not statistically different from what they were during 1988-1994 (5.4% and 0.38%, respectively). The prevalence of anti-HBc decreased among persons 6-19 years of age (from 1.9% to 0.6%; P < .01) and 20-49 years of age (from 5.9% to 4.6%; P < .01) but not among persons 50 years of age (7.2% vs 7.7%). During 1999-2006, the prevalence of anti-HBc was higher among non-Hispanic blacks (12.2%) and persons of "Other" race (13.3%) than it was among non-Hispanic whites (2.8%) or Mexican Americans (2.9%), and it was higher among foreign-born participants (12.2%) than it was among US-born participants (3.5%). Prevalence among US-born children 6-19 years of age (0.5%) did not differ by race or ethnicity. Disparities between US-born and foreign-born children were smaller during 1999-1996 (0.5% vs 2.0%) than during 1988-1994 (1.0% vs 12.8%). Among children 6-19 years of age, 56.7% had markers of vaccine-induced immunity.HBV prevalence decreased among US children, which reflected the impact of global and domestic vaccination, but it changed little among adults, and approximately 730,000 US residents (95% confidence interval, 550,000-940,000) are chronically infected.