OBJECTIVE: To assess the clinical characteristics and medication patterns of patients with schizophrenia treated with typical depot antipsychotics compared with oral antipsychotics in the usual care setting in Australia. METHODS: This was a prospective, single-site, observational study of 348 subjects with schizophrenia assessed at six-month intervals over three years. Data were collected via face-to-face interviews by research personnel and from external information systems to evaluate resource utilisation. The two groups were compared for demographic and clinical characteristics at baseline, co-therapy use, rate and average length of stay (ALoS) of hospitalisation over the three years. Analysis of variance was used to compare continuous variables, whereas the chi-square test was used for categorical outcomes. RESULTS: A total of 144 and 179 patients were treated with depot and oral antipsychotics, respectively. 25 patients were not treated with any antipsychotic medication, so were excluded from the analyses. Compared with oral users, depot patients were more likely to: have had more previous episodes of schizophrenia; have spent more days in hospital, be male; be less educated; be unemployed; be violent; and have experienced non-violent crimes. Approximately 50% of all depot users were treated with an oral antipsychotic supplement as co-therapy. A higher proportion of depot users were admitted and re-admitted to hospital throughout the study, with significant differences in year 2 and 3 (p <0.01, respectively). The ALoS was consistently higher in depot users compared with oral users over the three years. CONCLUSION: Patients treated with typical depot antipsychotics appear to be distinctly different from those treated with oral antipsychotics. Depot users were found to consume considerably more health care resources. This study indicates that there may be a subset of the schizophrenia population whose clinical needs are not currently well met by existing treatment options.