ObjectivesTo evaluate whether endometriosis and menstrual health education improves knowledge and attitudes among adolescents and is acceptable. MethodsWe conducted a cluster-randomised controlled trial in a Canadian school district. Eligible classes were grades 8–12, co-educational, and English. Classes were randomly assigned either to a 60-minute virtual menstrual health and endometriosis education program before (intervention) or after (waitlist control) primary data collection. The primary outcome was change in endometriosis knowledge from baseline to follow-up (∼4 weeks later, 6-item questionnaire). Secondary outcomes were changes in confidence in endometriosis knowledge, prioritisation of menstrual health knowledge, and comfort in discussing menstrual health, as well as intervention acceptability. The sexual health educator and statistician were masked. ResultsIn April and May 2021, 2 intervention classes and 2 control classes completed the study. In total, 71 students enrolled, and 48 were present on both baseline and follow-up days. Mean age was 15.7 ± 1.6 years, 55% identified as non-White ethnicities, and 53% were female. The knowledge score increased by 1.86 points in the intervention classes compared with 0.30 points in the control classes, with an estimated mean difference of 1.56 (95% CI 1.12–2.00). The intervention classes showed increased confidence in endometriosis knowledge, prioritisation of menstrual health knowledge, and comfort in discussing menstrual health, compared to the control classes. The mean acceptability index was 80 (SD = 10) in the intervention classes and 70 (SD = 20) in the control classes. ConclusionsA brief menstrual health and endometriosis education program improved knowledge and attitudes among adolescents, who considered the program acceptable.