BACKGROUND Pneumococcal vaccination after splenectomy for trauma decreases the incidence of overwhelming postsplenectomy infection. The optimal timing of vaccination has not been established. This study was conducted to determine whether timing of vaccination after splenectomy affects antibody response or survival after pneumococcal challenge. METHODS Sprague-Dawley rats were used for all experiments. Control rats (n=30) were divided into three equal groups and underwent splenectomy followed by sham vaccination 1, 7, or 42 days after splenectomy. Treated rats (n=66) were divided into three equal groups and underwent splenectomy followed by vaccination with polyvalent pneumococcal vaccine 1, 7, or 42 days after splenectomy. All rats then underwent intraperitoneal Streptococcus pneumoniae inoculation with the predetermined lethal dose for 50% of the population 10 days after vaccination. Rats were observed for a 72-hour period after inoculation, and mortality was recorded. Immunoglobulin G and immunoglobulin M antibody titers were determined before vaccination and before inoculation to determine antibody response. RESULTS Mortality was greater in the control group than in the treatment group (21 of 30 [70%] vs. 2 of 64 [3%]; p < 0.01). There were no differences in mortality within either the control group (1 day, 6 of 10; 7 days, 7 of 10; 42 days, 8 of 10; p=0.62) or the treatment group (1 day, 0 of 21; 7 days, 0 of 21; 42 days, 2 of 22; p=0.14). Immunoglobulin G and immunoglobulin M antibody responses were greater in vaccinated than in nonvaccinated rats. There was no effect of timing of vaccination on antibody response. CONCLUSIONS Pneumococcal vaccine reduces mortality from postsplenectomy infection. Timing of vaccination after splenectomy does not affect survival from a pneumococcal challenge or antibody response in rats. This study supports the practice of administering vaccine within 24 hours of splenectomy when vaccine cannot be administered before surgery.