OBJECTIVE: To compare psychiatric-related hospitalization and medication use in patients with schizophrenia, before and after initiation of risperidone long-acting injectable (RLAI) therapy. METHODS: Schizophrenia patients who participated in RLAI clinical trials in Canada were identified and their charts were retrospectively reviewed to assess hospitalization and medication use over identical periods before and after the initiation of RLAI therapy. RESULTS: Sixty-three charts were reviewed. The mean RLAI treatment period was 40.3 months with 52.4% of patients still receiving therapy at the time of the chart audit. The pre- and post-RLAI assessment periods were identical at 39.4 and 40.3 months, respectively (p = 0.8293). There were statistically significant differences in hospitalization before and after the initiation of RLAI therapy. After initiation of RLAI therapy fewer patients were hospitalized (52.4% prior to RLAI versus 4.8% during RLAI treatment, Relative Risk = 10.9, p <0.0001), fewer patients had more than one hospitalization (24% versus 0%, p <0.0001), the total duration of hospitalization days decreased by 99% (1558 versus 23, p <0.0001), the number of hospitalizations per patient decreased by 89% (0.9 versus 0.1, p <0.0001) and duration of hospitalization decreased by 98% (24.7 days per patient versus 0.4, p <0.0001). Furthermore, anticholinergic and anxiolytic use decreased from 81% of patients to 64% (p = 0.0459) and 57% to 35% (0.0198), respectively, with RLAI while sedative use was not significantly different (22% and 16% of patients used sedatives pre- and post-RLAI, respectively, p = 0.4967). CONCLUSIONS: RLAI had a significant impact on hospitalization of schizophrenia patients, offering a clear clinical benefit compared to traditional antipsychotic therapy. In addition, the significant decrease in hospitalization with RLAI offers the potential for substantial cost savings in the care of these patients.