BACKGROUND: Between 2001 and 2005 important changes were observed in expert opinion about the clinical management of patients with schizophrenia (SCZ) and agitation requiring an IM psychotropic, with a growing interest for IM atypical antipsychotics. STUDY OBJECTIVES: In an effort to acquire a typical, medically and psychiatrically unselected population of severely agitated patients with SCZ, we conducted a naturalistic study in an emergency setting, consecutively enrolling agitated patients who refused oral treatment. METHOD: Measures were collected prospectively for patients with acute agitation and schizophrenia (DSM IV diagnosis criteria) who consulted consecutively two ED: one in Belgium and the other one in Switzerland. Consent was obtained subsequently. A group of 40 patients with severe agitation and SCZ received olanzapine 10 mg IM. Efficacy and safety data (blood pressure, pulse, extrapyramidal symptoms) were assessed at baseline, two hours post-injection and at discharge. RESULTS: Significant reductions of agitation associated with good tolerance were observed two hours after the first IM olanzapine (PANSS EC declined from 28.6 +/- 4.13 to 16.8 +/- 4.8). Only 5% of patients required a second IM olanzapine. The absence of clinically significant extrapyramidal and cardiovascular side effects is promising, but considering the statistically significant reduction of systolic and diastolic blood pressure and pulse, vital signs should be checked especially in the first 2 hours post injection. CONCLUSIONS: This naturalistic study suggest a promising efficacy and safety balance of intramuscular olanzapine in patients with acute agitation and schizophrenia in emergency.