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Background  Armed conflicts are associated with a wide range of impacts on the mental health of children and adolescents. We evaluated the effectiveness of a school-based intervention aimed at reducing symptoms of posttraumatic stress disorder, depression, and anxiety (treatment aim); and improving a sense of hope and functioning (preventive aim).    Methods  We conducted a cluster randomized trial with 329 children in war-affected Burundi (aged 8 to 17 (mean 12.29 years, standard deviation 1.61); 48% girls). One group of children (n = 153) participated in a 15-session school-based intervention implemented by para-professionals, and the remaining 176 children formed a waitlist control condition. Outcomes were measured before, one week after, and three months after the intervention.    Results  No main effects of the intervention were identified. However, longitudinal growth curve analyses showed six favorable and two unfavorable differences in trajectories between study conditions in interaction with several moderators. Children in the intervention condition living in larger households showed decreases on depressive symptoms and function impairment, and those living with both parents showed decreases on posttraumatic stress disorder and depressive symptoms. The groups of children in the waitlist condition showed increases in depressive symptoms. In addition, younger children and those with low levels of exposure to traumatic events in the intervention condition showed improvements on hope. Children in the waitlist condition who lived on their original or newly bought land showed improvements in hope and function impairment, whereas children in the intervention condition showed deterioration on these outcomes.    Conclusions  Given inconsistent effects across studies, findings do not support this school-based intervention as a treatment for posttraumatic stress disorder and depressive symptoms in conflict-affected children. The intervention appears to have more consistent preventive benefits, but these effects are contingent upon individual (for example, age, gender) and contextual (for example, family functioning, state of conflict, displacement) variables. Results suggest the potential benefit of school-based preventive interventions particularly in post-conflict settings.    Trial registration  The study was registered as  ISRCTN42284825

School-based mental health intervention for children in war-affected Burundi: a cluster randomized trial