Objective: Current United States immunization recommendations for adolescents include vaccines against tetanus, diphtheria and pertussis (Tdap), human papillomavirus (HPV), and Neisseria meningitidis serogroups A, C, W-135, and Y. In this Phase IV study, we primarily investigated the impact of concomitant administration of a quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM) with Tdap and HPV vaccines, in terms of immunogenicity to Tdap antigens and overall reactogenicity. Methods: A total of 801 healthy adolescents aged 10-18 years were randomized to one of two groups to receive either MenACWY-CRM or a placebo, co-administered with Tdap and a quadrivalent HPV vaccine (HPV4). Antibody responses to the Tdap antigens, as well as to meningococcal serogroups A, C, W-135, and Y, were assessed at one month post-vaccination. Safety and adverse events were monitored throughout the study. Results: One month post-vaccination, 95% and 99% of subjects in the MenACWY-CRM group had seroprotective antibody levels (≥1.0 IU/mL) against the diphtheria and tetanus toxoids, respectively, compared with 82% and 98% in the placebo group. Ratios of geometric mean concentrations of antibodies against pertussis antigens pertussis toxin, filamentous hemagglutinin and pertactin for the MenACWY-CRM group versus placebo were 1.01, 0.84, and 0.82, respectively. Predetermined non-inferiority criteria for immunological responses against all Tdap antigens were met. Co-administration of a single dose of MenACWY-CRM was well tolerated and elicited robust antibody responses against the four meningococcal serogroups, with 77%, 84%, 95% and 86% of subjects having seroprotective human complement serum bactericidal activity (titers ≥8) against serogroups A, C, W-135, and Y, respectively, one month post-vaccination. Conclusions: Collectively, these results demonstrate that the MenACWY-CRM, Tdap and HPV4 vaccines can be administered at the same visit without compromising Tdap immune responses or increasing reactogenicity. [The study is registered with ClinicalTrials.gov, number NCT01424644].