Current European and US guidelines for recombinant hepatitis B vaccine (rHBV) after hematopoietic-cell transplantation (HCT) vary. The European Group for Blood and Marrow Transplantation (EBMT) recommends rHBV starting 6 to 12 months after HCT. Immunization is optional in the Centers for Disease Control and Prevention (CDC) guidelines. Nevertheless, rHBV is required for re-entry to school and certain workplaces. To determine the immunogenicity of rHBV following HCT, the prevaccine and postvaccine titers of 292 allogeneic transplant recipients who were immunized with rHBV were analyzed. Immunization was initiated in patients off immunosuppression who achieved specific minimal milestones of immune competence. Overall, 64% of patients seroconverted. In multivariate analyses, response was adversely affected by age older than 18 years (P < .01) and history of prior chronic graft-versus-host disease (GVHD; P < .001) but not by donor type or by use of T-cell depletion, adoptive immunotherapy, or rituximab. By comparison, 89% of rHBV nonresponders mounted a 3-fold or greater rise in polio titers following 3 doses of inactivated poliovirus. These data demonstrate that the rate of seroconversion following rHBV is lower in allogeneic HC transplant recipients compared with age-matched healthy controls. The data emphasize the need to document prevaccine and postvaccine titers to ensure response and suggest that immunization guidelines based on time interval from HCT, irrespective of immune competence, may not ensure adequate protection against certain vaccine-preventable diseases.