AbstractAntipsychotics are often prescribed to children and adolescents, mostly off-label. We aimed to assess adherence to recommendations of guidelines for antipsychotic prescription. We reviewed 436 medical records from 155 clinicians from 26 clinics within three Dutch child and adolescent psychiatry organizations (n = 398 outpatient, n = 38 inpatient care). We assessed target symptoms, diagnostic process, prior and concomitant treatment, and consideration of contra-indications. Multiple logistic regression assessed the role of age, sex, and psychiatric diagnosis on adherence to three main recommendations: to (1) prescribe antipsychotics only after other treatments proved insufficient, (2) always combine antipsychotics with psychosocial interventions, and (3) not prescribe multiple antipsychotics simultaneously. Most patients received off-label antipsychotics. Main target symptoms were inattention/hyperactivity (25%), aggression (24%), and other disruptive behaviors (41%). Most patients underwent diagnostic evaluation before the first prescription; however, screening of contra-indications was low (0.2–19%). About 84% had previously received psychosocial treatment and 48% other psychoactive medication, but 9% had not received any treatment. Notably, only 37% continuously received concomitant psychosocial treatment. Simultaneous use of multiple antipsychotics occurred in 3.2%. Younger children were at higher risk of non-adherence to guideline recommendations regarding prior and concomitant treatment, children with autism spectrum disorder or attention-deficit/hyperactivity disorder more likely not to receive concomitant psychosocial treatment. Sex did not significantly affect adherence. Our findings implicate insufficient adherence to important recommendations regarding antipsychotic use in children and adolescents. Especially younger children are at higher risk of receiving suboptimal care. There is an urgency to consistently offer psychosocial interventions during antipsychotic treatment.