Background.  Data on the age-specific prevalence of Epstein–Barr virus (EBV) infection are relevant for determining when to administer a prophylactic vaccine. Comparison of demographic groups could identify factors associated with its acquisition.

Methods.  The National Health and Nutrition Examination Surveys (NHANES) examine a representative sample of the US population. Serum specimens from NHANES participants 6–19 years old were tested for EBV antibody by enzyme immunoassay (EIA). A random portion was also tested by indirect immunofluorescence (IFA). Prevalence estimates and risk-factor comparisons used demographic data and sampling weights in logistic regression models.

Results.  Serum specimens collected between 2003 and 2010 from 9338 individuals participating in NHANES were tested. The concordance between EIA and IFA findings was 96.7%. The overall age-adjusted EBV antibody prevalence declined from 72% in 2003–2004 to 65% in 2009–2010 (P = .027). The prevalence in 2009–2010 by age group was as follows: 6–8 years, 50%; 9–11 years, 55%; 12–14 years, 59%; 15–17 years, 69%; and 18–19 years, 89%. Within each race/ethnicity group, younger age, health insurance coverage, higher household income, and education level were significantly associated with a lower prevalence of EBV antibody.

Conclusions.  The EBV antibody prevalence declined in US individuals aged 6–19 years from 2003–2004 to 2009–2010, mainly because of the decrease among non-Hispanic white participants. The declining antibody prevalence over time and the consistently high observed prevalence among participants aged 12–19 years support broad use of EBV vaccine before 12 years of age.