Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n = 130) to immunization with the MCC vaccine was investigated. Asplenic individuals had a significantly lower geometric mean titer (GMT) (157.8; 95\% confidence interval CI, 94.5 to 263.3) of bactericidal antibody in serum (SBA) than an age-matched control group (n = 48) (1448.2; 95\% CI, 751.1 to 2792.0). However, 80\% of asplenic individuals achieved the proposed protective SBA titer of \textgreater or =8. No differences were observed between the two groups in the serogroup C-specific immunoglobulin G geometric mean concentration. A significant reduction in SBA GMT or the number of responders achieving an SBA titer of \textgreater or =8 was observed if the reason for splenectomy was a medical cause or if MCC vaccination occurred \textless10 years after splenectomy. Individuals (n = 29) who did not achieve an SBA titer of \textgreater or =16 were offered a second dose of MCC vaccine. Analysis of the SBA response revealed that 61\% (14 of 23) of the individuals who received a second dose achieved a protective titer. In total, 93\% of asplenic individuals achieved a titer of \textgreater or =8 following MCC vaccination (one or two doses combined). We recommend that, following vaccination of asplenics, either the level of functional antibody should be determined, with a second dose of MCC vaccine offered to nonresponders, or two doses of MCC vaccine should be routinely offered.