OBJECTIVE: To assess the frequency and management of extrapyramidal symptoms (EPS), sexual dysfunction related adverse events (SD-RAEs) and weight changes which may impede optimal outcomes in schizophrenic patients under antipsychotic treatment and to perform an economic evaluation. METHODS: A cross-sectional study was carried-out by 61 Spanish psychiatrists (the EIRE Study Group). Outpatients meeting DSM-IV criteria for schizophrenia and taking a single atypical antipsychotic (olanzapine, quetiapine or risperidone) for at least four weeks were evaluated. EPS, SD-RAEs and weight changes were assessed using a modified-UKU scale, which included a question for assessing management of adverse events. Cost of antipsychotic and EPS therapies obtained of wholesaler price in 2001 were used to perform a cost-effectiveness analysis comparing the cost per patient free of EPS between drugs. RESULTS: Five hundred five evaluable patients were assessed. The average doses were those seen commonly in the clinical setting: 13.5 mg/d (OLAN), 360.5 mg/d (QUE) and 5.3 mg/d (RIS). Tolerability and economic evaluation outcomes for olanzapine (n = 228), quetiapine (n = 43) and risperidone (n = 234) were: 35.8%, 39.5% and 55.1% with EPS (2:p <0.05 risperidone vs. olanzapine); 35.3%, 18.2% and 43.2% with SD-RAEs (?2:p <0.05 risperidone vs. quetiapine); 74.5%, 13.5% and 53.4% with weight gain (?2:p <0.05 risperidone & olanzapine vs. quetiapine); daily therapy cost was 3.67, 2.72 and 1.96 euros; daily cost per patient without EPS was 5.72, 4.38 and 4.50 euros. EPS and SD-RAEs were dose-related but weight gain was not. SD was more frequent in men. Add-on therapy for EPS was required by 20.3%, 16.4% and 7,1%, respectively of risperidone-, olanzapine- and quetiapine-treated patients. SD and weight changes modified psychiatrist-patient management in only 17.2%, 10.2% and 0.0%, and in 2.1%, 9.0% and 0.0%, respectively. CONCLUSION: EPS, SD-RAEs and weight changes are common side effects with atypical antipsychotics. Cost per patient without EPS is higher with olanzapine than with risperidone or quetiapine.