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ABSTRACTIn 2007, recommendations were proposed for the molecular typing of meningococci. Multilocus sequence typing (MLST) was recommended to guide national and international disease management and facilitate studies of population biology and evolution. Sequencing of porAvariable regions (VRs) 1 and 2 and the fetAVR was recommended for monitoring antigenic distribution and investigating potential outbreaks. porBcharacterization was recommended if further resolution was required. Several investigational “group B” meningococcal vaccines, including two in the advanced stages of development, incorporate factor H-binding protein (fHBP). The requirement for routine surveillance of fhbpplaces additional pressure on reference laboratories, both financially and in terms of labor. This study investigated the optimal and most efficient molecular typing schemes for (i) routine meningococcal characterization and (ii) the investigation of potential outbreaks, in conjunction with routine surveillance of fhbp.All invasive disease isolates received by the Health Protection Agency Meningococcal Reference Unit between July 2007 and June 2008 (n= 613) were characterized in terms of capsular group, porA, fetAVR, fhbp, and sequence type (ST). Following capsular grouping and porAgenosubtyping, several predominant capsular group-porAcombinations were identified. The levels of additional resolution afforded by fetAand fhbpwere comparable and partially complementary. fhbpconstitutes an effective substitute for fetAas a routine marker of antigenic distribution, thereby reducing costs in conjunction with fhbpsurveillance. MLST afforded markedly superior resolution overall and is the optimal scheme for investigating outbreaks in which (i) typing data are unavailable for the index case or (ii) the index case possesses a known, predominant capsular group-porArepertoire.