Background/Objective: Persons with spinal cord injury (SCI) are predisposed to develop pneumonia. This study was undertaken to determine the effect of revaccination with the pneumococcal vaccine on the immune response and the frequency of adverse reactions in this population. Methods: An enzyme-linked immunosorbent assay was used to measure immunoglobulin G to selected pneumococcal capsular polysaccharides on sera collected from 23 persons who were revaccinated 5 years after primary vaccination. Sera were collected just prior to, 1 month, and 1 year following revaccination. Functional activities of serotype-specific antibodies were determined by opsonophagocytosis assays. Results: Several subjects maintained protective antibody concentrations at baseline. Increases in antibody concentrations were observed for all serotypes at 1 month and 1 year. Opsonophagocytic activity increased over baseline when evaluated 1 month and 1 year after revaccination, and a significant positive correlation was observed between antibody concentration and opsonophagocytic activity at all 3 time points. Three persons (13%) experienced transient and self-limited local swelling and pain at the injection site following revaccination. Conclusions: Protective antibody may be present in some persons for at least 5 years after vaccination. Revaccination induces a secondary surge in antibody concentration and opsonophagocytic activity that varies according to serotype but may be of lesser magnitude than the primary response. Revaccination of persons with SCI is not associated with significant adverse effects. Whether revaccination is needed beyond 5 years will require additional investigation. © 2008 by the American Paraplegia Society.