Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count was 192×10⁶ cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3–36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10^-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200×10⁶ cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10^-4). Younger age may favor CD4 cell restoration because of preserved thymic function