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Background The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by the World Health Organization and the United Nations Educational, Scientific and Cultural Organization. Objectives To evaluate the effects of If I Were Jack on the avoidance of unprotected sex and other sexual health outcomes. Design A cluster randomised trial, incorporating health economics and process evaluations. Setting Sixty-six schools across the four nations of the UK. Participants Students aged 13–14 years. Intervention A school-based, teacher-delivered, gender-transformative RSE intervention (If I Were Jack) versus standard RSE. Main outcome measures Self-reported avoidance of unprotected sex (sexual abstinence or reliable contraceptive use at last sex) after 12–14 months. Secondary outcomes included knowledge, attitudes, skills, intentions and sexual behaviours. Results The analysis population comprised 6556 students: 86.6% of students in the intervention group avoided unprotected sex, compared with 86.4% in the control group {adjusted odds ratio 0.85 [95% confidence interval (CI) 0.58 to 1.26], p = 0.42}. An exploratory post hoc analysis showed no difference for sexual abstinence [78.30% intervention group vs. 78.25% control group; adjusted odds ratio 0.85 (95% CI 0.58 to 1.24), p = 0.39], but more intervention group students than control group students used reliable contraception at last sex [39.62% vs. 26.36%; adjusted odds ratio 0.52 (95% CI 0.29 to 0.920), p = 0.025]. Students in schools allocated to receive the intervention had significantly higher scores on knowledge [adjusted mean difference 0.18 (95% CI 0.024 to 0.34), p = 0.02], gender-equitable attitudes and intentions to avoid unintended pregnancy [adjusted mean difference 0.61 (95% CI 0.16 to 1.07), p = 0.01] than students in schools allocated to receive the control. There were positive but non-significant differences in sexual self-efficacy and communication skills. The total mean incremental cost of the intervention compared with standard RSE was £2.83 (95% CI –£2.64 to £8.29) per student. Over a 20-year time horizon, the intervention is likely to be cost-effective owing to its impact on unprotected sex because it would result in 379 (95% CI 231 to 477) fewer unintended pregnancies, 680 (95% CI 189 to 1467) fewer sexually transmitted infections and a gain of 10 (95% CI 5 to 16) quality-adjusted life-years per 100,000 students for a cost saving of £9.89 (95% CI –£15.60 to –£3.83). Limitations The trial is underpowered to detect some effects because four schools withdrew and the intraclass correlation coefficient (0.12) was larger than that in sample size calculation (0.01). Conclusions We present, to our knowledge, the first evidence from a randomised trial that a school-based, male engagement gender-transformative RSE intervention, although not effective in increasing avoidance of unprotected sex (defined as sexual abstinence or use of reliable contraception at last sex) among all students, did increase the use of reliable contraception at last sex among students who were, or became, sexually active by 12–14 months after the intervention. The trial demonstrated that engaging all adolescents early through RSE is important so that, as they become sexually active, rates of unprotected sex are reduced, and that doing so is likely to be cost-effective. Future work Future studies should consider the longer-term effects of gender-transformative RSE as students become sexually active. Gender-transformative RSE could be adapted to address broader sexual health and other settings. Trial registration This trial is registered as ISRCTN10751359. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (PHR 15/181/01) and will be published in full in Public Health Research; Vol. 11, No. 8. See the NIHR Journals Library website for further project information. Plain language summary Adolescent pregnancy is often thought to be an issue for young women alone, but it is important to engage young men to tackle the problem and find solutions. The If I Were Jack intervention was especially designed to engage with boys as well as girls aged 14 years and to promote positive masculinity and gender equality to prevent adolescent pregnancy and promote positive sexual health. It uses tailored interactive films and resources, made with the help of students and teachers, to make it relevant to each of the four UK nations. This relationship and sexuality education intervention encourages adolescents to avoid unprotected sex by delaying sexual activity until they feel ready and to use reliable contraception once sexually active. It also promotes knowledge, attitudes (such as beliefs about gender and masculinities), skills and intentions for safe and pleasurable relationships. In this trial, we compared students in 33 schools randomly allocated to deliver the intervention with students in 33 schools that continued with their usual relationship and sexuality education practices. Four schools withdrew, two because of COVID-19 school closures. This left a total of 6556 students who completed questionnaires at the start of the study and 12–14 months later. Responses from all these students showed that If I Were Jack had a positive impact on knowledge, attitudes and intentions required for safe and pleasurable relationships, but did not have a significant effect on overall avoidance of unprotected sex. This was because the intervention had no effect on delaying sexual activity. However, we found that the intervention was effective in increasing the use of reliable contraception as students became sexually active, as well as for those who already were sexually active prior to receiving the intervention. We also found that If I Were Jack was likely to provide value for money by reducing unintended pregnancies and improving sexual health. Scientific summary Background The need for relationship and sexuality education (RSE) to especially engage with young men and boys to promote positive sexual health for all, and to be gender transformative to challenge the gender inequalities that underlie young women’s generally poorer sexual health outcomes (especially in relation to sexual violence, adolescent pregnancy and sexually transmitted infections), is widely endorsed by the World Health Organization and the United Nations Educational, Scientific and Cultural Organization, among others. Objectives The JACK trial evaluated the effectiveness and cost-effectiveness of the If I Were Jack intervention, a schools-based RSE intervention, which is designed to especially engage young men as well as young women and promote joint responsibility in preventing adolescent pregnancy by avoiding unprotected sex and in promoting positive sexual health and relationships. We assessed whether there would be higher rates of self-reported avoidance of unprotected sex (either by remaining sexually abstinent or by using a reliable form of contraception) among students in schools allocated to use If I Were Jack than among those in schools that continued with their usual RSE. Design We undertook a multicentre, parallel-group cluster randomised trial of the If I Were Jack intervention with schools as the unit of randomisation. We incorporated a health economic cost–consequences analysis and process evaluation. Setting The trial was conducted in secondary-level schools across the four nations of the UK. Recruitment We sampled schools from Department of Education-listed secondary schools in each nation of the UK (Northern Ireland, Wales, Scotland and England), with consideration of the socioeconomic status of schools [based on the proportion of students eligible for free school meals (FSM) as indicated by the School Meal Census]. In each nation, eligible schools were stratified into two levels according to FSM eligibility rates (schools above and below the median national percentage of FSM for all eligible schools). Independent private, special, and Irish/Welsh-medium and Scottish Gaelic schools and schools with