Abstract Background In 2018, meningococcal ACWY-TT vaccine (MenACWY-TT) was offered to adolescents in the Netherlands within the National Immunization Programme at 14 years of age. A questionnaire study assessed the tolerability of this vaccine. Methods Five thousand adolescents were invited to participate and to fill in two questionnaires about systemic events in the week before vaccination and local reactions and systemic events in the week after vaccination. Frequencies of local and systemic adverse events in the week after vaccination were calculated. Association between the occurrence of systemic symptoms in the week before and after the vaccination was tested by using generalized mixed models (GLMM). Results Of all adolescents, 139 returned one or both questionnaires. Any local reaction within 7 days after vaccination was reported by 55.6% of the adolescents. Pain (50%) and reduced use of the injected arm (21.3%) were most often reported. Any systemic event was reported by 67.6% of the participants, with myalgia as the most often reported event (37.0%). Compared with the week before vaccination, there were no increased odds of experiencing systemic symptoms in the week after vaccination (OR 0.95; 95%CI 0.40–2.27). Conclusions After vaccination with MenACWY-TT vaccine, most adolescents reported one or more adverse events, which were mostly mild and transient. Systemic symptoms were not reported more often in the week after compared to the week before vaccination. Unfortunately, due to a low response rate we were not able to detect the absolute elevated risks the sample size calculation was based on. However, despite limited data, our results are in line with results from prelicensure data, and indicate that MenACWY-TT vaccination is well tolerated in adolescents.