Background: HIV-infected youth are at risk of hepatitis B infection and should be vaccinated. Previous reports suggest reduced response to standard hepatitis B vaccine regimens. Methods: HIV-infected youth, aged 12 to younger than 25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B, 20 μg HBsAg; Arm 2: Engerix B (GlaxoSmithKline, Rixensart, Belgium), 40 μg; and Arm 3: Twinrix (GlaxoSmithKline, Rixensart, Belgium), 20 μg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at Weeks 0, 4, and 24. Results: Characteristics of evaluable patients (n = 336) at entry were similar in the study arms. At enrollment, median CD4 T-cell count was 460 cells/mm (interquartile range, 305-668); 13% were less than 200 cells/mm. Among Engerix B, 20-μg recipients, 60.4% responded to vaccine (HBsAb 10 IU/mL or greater at Week 28). Improved vaccine response was seen in recipients of Engerix B, 40 μg (73.2% versus Arm 1, P = 0.04) and Twinrix (75.4% versus Arm 1, P = 0.02). In multivariate analysis, only baseline CD4 T-cell count and study arm were independent predictors of vaccine response. Conclusions: In HIV-infected youth, a three-dose vaccination regimen with Engerix B, 40 μg, or Twinrix and higher baseline CD4 T-cell counts were independently associated with improved vaccine response. © 2011 Lippincott Williams & Wilkins.