Young children and allogeneic hematopoietic cell transplantation (HCT) recipients respond poorly to polysaccharide antigens, rendering them susceptible to severe infections because of encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults, P < .001). Overall response to HIB was 86%, including 77% of PNCRM7 nonresponders. Although PNCRM7 response was adversely affected by older age (P < .001), individuals > or =50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multicenter trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted.