Objective: to evaluate the health results and the costs related to the available antipsychotics, with emphasis on olanzapine, in naturalistic outpatient settings. Methods: 572 patients with schizophrenia (ICD-10 or DSM-IV) who began or changed to an oral, antipsychotic were enrolled in blocks of ten: 5 patients for olanzapine and 5 for another antipsychotic, according to the prescription at that time. The effectiveness was measured by the mean change in score on the Global Clinical Impression of Severity of illness Scale (GCI-S). "Clinical response" was defined as the decrease ≥" 2 points on the GCI-S if the baseline score was ≥" 4 and the decrease ≥" 1 if the baseline was ≤" 3. "Minimally symptomatic" was defined as reaching a score of 1 or 2 on the GCI-S after the baseline. Adverse events resulting from the treatment were recorded, along with the use of any concomitant medication and the causes of discontinuation of the medication. Results: The SOHO Andean Region enrolled 272, 97 and 65 patients in monotherapy with olanzapine, typical antipsychotics (TA) and risperidone respectively. Both olanzapine and risperidone were more effective than the TA in improving the general, positive and negative symptoms at 12, 24, and 36 months, but only olanzapine showed a statistically significant difference vs TA in depressive and cognitive symptoms. Less patients on olanzapine developed extrapyramidal symptoms (EPS) and adverse sexual events. The patients on olanzapine demonstrated the lowest rate of tardive dyskinesia at 3 years. More patients on olanzapine gained weight with a statistically significant difference vs risperidone and TA. The mean weight gain with olanzapine was 5 kg and the greatest increase was recorded in the first 12 months of treatment. Conclusions: olanzapine, but not risperidone, was more effective than typicals improving depressive and cognitive symptoms with statistical difference. Olanzapine was better tolerated in terms of EPS, tardive dyskinesia and sexual function impairment. A greater weight gain was recorded with olanzapine; however, the discontinuation rate due to intolerability was the lowest. These results support the greater benefits of Atypicals in terms of effectiveness and tolerability. ©INNN, 2007.