Background: Suicidal ideation and suicide attempts pose a serious public health concern among adolescents and young adults. School-based suicide prevention programs are a key tool for addressing this problem. However, more research is necessary to assess their effectiveness, acceptability, and safety. In response, the HEYLiFE suicide prevention program was developed to enhance help-seeking, reduce stigma towards suicidal peers and diminish risk factors for suicidality. This article presents the evaluation findings of the HEYLiFE program in German secondary schools. Methods: We conducted a randomized-controlled trial measuring short-term pre-post within-group effects in the intervention group only and mid-term effects at 6-months-follow-up in the intervention and a waitlist control group. Schools were assigned randomly to the intervention or control group (no blinding). We recruited students ≥12 years of age in secondary schools. Primary outcomes were knowledge about suicidality, attitudes towards suicidality, stigma towards a suicidal peer, help-seeking intentions and behaviours, as well as risk factors for suicidality. The data was analysed with linear mixed models andgeneralized linear mixed models. Results: N = 745 students participated (n= 353 intervention group, n = 392 control group). We observed favourable short-term effects on knowledge, attitudes towards suicidality and fear towards a suicidal peer. Unexpectedly, the program also led to an increase in desire for social distance and a decrease in prosocial emotions towards a suicidal peer. The mid-term effects of the program were exclusively favourable, resulting in enhanced attitudes towards help-seeking while protecting from a sharper rise in risk-factors for suicidality and from an increase in social distance. The program had more favourable effects on females than on males. The program was well-received by the students, and no serious adverse events were reported. Conclusions: These findings demonstrate the effectiveness of the HEYLiFE universal suicide prevention program in addressing variables associated with suicidal ideation and suicide attempts among adolescents on the mid-term. Short-term negative effects on stigma and more negative effects on males should be addressed in the future. Future evaluation studies should examine the effects on suicidality and its effectiveness on populations at high risk.