Background <p>Schools are suitable settings to prevent suicide among adolescents. We tested the effectiveness of a school-based program to reduce suicidal ideation (SI) (Reframe-IT +). It encompasses 13 sessions (eight internet-based and five face-to-face sessions).</p> Methods <p>We conducted a cluster RCT among students aged 13–18. Twenty-one schools were randomized (Intervention Group (IG), <i>N</i> = 47); Control Group (CG), <i>N</i> = 48)). The primary outcome was SI. Secondary outcomes were depressive and anxiety symptoms, psychotic experiences, hopelessness, and emotion regulation strategies (cognitive reappraisal, and emotion suppression), problem-solving skills and behavioral activation. Outcomes were assessed at baseline, post-intervention, 3-month, 6-month, and 10-month follow-up). Trial registration: Clinical Trials NCT05229302. Registered on Registered on February 8, 2022.</p> Results <p>We found a non-significant overall intervention effect on SI across follow-up assessments, but significant overall intervention effects on depressive and anxiety symptoms and psychotic experiences. Moreover, we found time-specific reductions immediately after the intervention and close to it, particularly for depressive and anxiety symptoms, hopelessness, behavioral activation and cognitive re-appraisal. The change favoring the IG of cognitive re- appraisal was also significant at 10&#xa0;months follow-up.</p> Conclusions <p>Our results suggest that Reframe-IT + reduces depressive and anxiety symptoms and psychotic experiences in the long term. Less promising results were related to suicidal ideation prevention. Further research is needed with a larger sample size.</p>