Objective: To compare the efficacy and tolerability of olanzapine and haloperidol in treating patients with amphetamine-induced psychotic disorder. Design: A double-blind randomized controlled trial. Setting: Phramongkutklao Hospital. Patients: Fifty-eight patients experiencing their episode of emphetamine-induced psychotic disorder and satisfying the eligible criteria were randomly assigned to olanzapine (N = 29) or haloperidol (N = 29) in a 1:1 (haloperiodol:olanzapine) ratio. Intervention: All patients began therapy with 5-10 mg/day of study drug; after each 7-day period, the study drug could be adjusted in 5-mg increments or decrements within the allowed dose range of 5-20 mg/day during 4-week study period. Results: Clinical response was seen in both treatment groups since first week. 93% of the olanzapine patients (N = 27 of 29) and 79.3% of the haloperidol patients (N = 23 of 27) were clinically improved at endpoint. These differences were not statistically significant (Fisher's exact p = 0.25). The Simpson-Angus total score change from baseline to endpoint reflected an unchanged in extrapyramidal symptoms among the olanzapine-treated patients (median = 0.0, range = 0.0). In contrast, a worsening occurred among the haloperidol-treated patients (median = 0.2, range = 0.0-3.1). The differences of mean change in SAS significantly favored olanzapine (p<0.01). Change to endpoint on the Barnes global scores showed that olanzapine-treated patients' scores were closely to baseline (median = 0.0, range = -1.0-0.0), whereas haloperidol-treated patients' scores worsened from baseline (median = 0.0, range = -1.0-3.0). This treatment difference was statistically significant (p = 0.02). Conclusion: Both olanzapine and haloperidol were efficacious in the treatment of patients with amphetamine-induced psychotic disorder. Olanzapine showed superior in treatment safety, frequency and severity of extrapyramidal symptoms, when compared to conventional neuroleptic haloperidol.