Objectives: This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults (quadrivalent polysaccharide-CRM197 conjugate vaccine containing meningococcal serogroups A, C, W, and Y). Methods: Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific to serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Results: Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (n=297) or a saline placebo (n=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Conclusions: Findings of this first study on a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.