The efficacy of pneumococcal vaccine given after splenectomy lacks experimental validation. Adult CD-1 male mice that received type III pneumococcal capsular polysaccharide vaccine 1 μg IP, 48 hours postsplenectomy and 7 days before challenge with aerosolized type IIIStreptococcus pneumoniaehad a significantly higher mortality (96%) compared to immunized controls (64%) (p< 0.002). The vaccine protected immunized sham-operated mice compared to unimmunized controls (p< 0.015). Mice immunized 7 days before splenectomy were equally protected when compared to immunized sham-operated mice (p= NS). All deaths were secondary to culture-proven pneumococcal infection. These findings corroborate previous experimental and clinical studies demonstrating an impaired immunologic response and increased susceptibility to infection in asplenic individuals. Pneumococcal vaccines should be given before nonemergent splenectomy. Alternatives to splenectomy should be considered for patients with traumatized spleens where possible.