Background: The aim was to perform a meta-analysis on the efficacy, safety and tolerability of antipsychotic drugs in adolescents aged between 13 and 17 suffering from Schizophrenia. Methods: Enclosed studies -were multicentric, randomized, double-blind clinical trials; -included only adolescents (aged 13-17) with DSM-IV diagnosis of Schizophrenia; -used standardized scales to assess efficacy, safety and tolerability of antipsychotics. Results: All treatments resulted in significant improvements in Positive and Negative Syndrome Scale (PANSS) total score (p < 0.001), in PANSS positive subscale score (p < 0.001) and in Clinical Global Impression Scale-Severity of Illness score (p < 0.001) at the endpoint. Patients with a considerable weight gain were significantly higher in the Olanzapine-treated group. Data about extrapyramidal side-effects were not available for Olanzapine. Risperidone group was associated with a significantly major incidence of akathisia, tremor and dystonic events than controls. High dose of Aripiprazole was associated with a significant major incidence of tremor and Parkinsonism (p < 0.01) than controls. Conclusions: Results demonstrated that antipsychotic treatment with Risperidone, Olanzapine or Aripiprazole in adolescents affected by Schizophrenia led to significant improvements in symptomatology. A pharmacological treatment for adolescents suffering from Schizophrenia must fulfil several prerequisites, to grant the most favourable outcomes, avoiding acute and long term side-effects. Treatment with a 10 mg daily dose of Aripiprazole was associated with the lowest incidence of extrapyramidal symptoms and showed no significant weight gain. If a treatment with antipsychotic drugs associated with significant weight gain as Olanzapine or Risperidone is needed, compensative measures should be soon considered. Psychopharmacology Bulletin. 2010; 43(2):45-66