OBJECTIVES: This randomized, multicenter, open-label, parallel clinical trial was carried to compare the therapeutic efficacy and the proportion of successful switch between 'direct switching method' and 'start-tapering switching method' when switching an antipsychotic to olanzapine. METHODS: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10 from 13 hospitals, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For 'direct switching method' group, previous antipsychotics were abruptly discontinued and 10mg of olanzapine was administered, whereas for 'start-tapering switching method' group, initially 10mg of olanzapine was administered and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20mg. The therapeutic efficacy was measured with PANSS, BPRS, and CGI-Severity. A successful switching was defined as the completion of the 6 week trial without either worsening of the symptom(i.e. CGI-S score becomes worse twice consecutively) or the exacerbation of extrapyramidal symptoms(i.e. Simpson-Angus Scale scores becomes worse). RESULTS: 103 schizophrenic patients were participated in this study. There were no differences in baseline characteristics such as the demographic variables, the severity of symptoms, the history of previous antipsychotics treatments, the dosage of olanzapine used and the compliance between two groups. The proportion of successful switch was 71.1% for "direct switching method" and 82.2% for "start-tapering switching method", and there was no significant difference between the two switching methods. Also response rates to olanzapine based on total PANSS total scores were not different between the two groups(26.9% vs. 31.1%). At the time of completion of the trial, the scores of PANSS total, PANSS subscales, CGI-S and BPRS have significantly decreased after switching to olanzapine. But the changes of all scales measuring therapeutic efficacy in both endpoint and weekly analyses were not significantly different between the two switching methods. CONCLUSION: Although this study trial has many limitations and problems as an open clinical trial, the results may suggest that there were no significant differences between the two switching methods in the therapeutic efficacy. It was also found that the additional therapeutic benefits could be obtained by switching their antipsychotics to olanzapine.