BACKGROUND: Neisseria meningitidis is a leading cause of meningitis and sepsis worldwide. Since 1981, a tetravalent meningococcal polysaccharide vaccine has been available in the US but it has been limited to high-risk patients and outbreak settings. In 2005, a tetravalent polysaccharide meningococcal conjugate vaccine (MCV4) was licensed for routine use in the US. OBJECTIVE: To assess the immunogenicity and safety of MCV4, and to extrapolate the anticipated clinical effectiveness of MCV4 using data from other polysaccharide conjugate vaccination programs. METHODS: All published controlled studies of MCV4 immunogenicity, safety and cost-effectiveness are analyzed. Publicly-available clinical trial data and the Advisory Committee on Immunization Practices guidelines were also reviewed. CONCLUSION: MCV4 is as safe and immunogenic as the previously available polysaccharide vaccine, and seems to provide longer lasting protection against meningococcal disease. Long-term studies are continuing and will shed further light on the effectiveness of MCV4 at the population level.