Risperidone long-acting injectable (R-LAI) was the first of the ‘atypical’ antipsychotic drugs with delayed release to be marketed worldwide for the treatment of schizophrenia. This strategy was envisaged to deliver a primary advantage over conventional oral drugs but could not be demonstrated ahead of marketing approval as R-LAI was mainly assessed against placebo for that purpose. A risk-sharing agreement was reached between the manufacturer and the French National Health Pricing Authority – The Economic Committee on Health Care Products (CEPS), under which coverage would be ensured following demonstration of cost minimization in real terms. OBJECTIVES: To assess whether R-LAI use was associated with a decreased risk of hospitalization and provide data for risk-sharing agreement and coverage. METHODS: A cohort with a ‘dynamic exposure’ methodology was used to assess the relative effectiveness of R-LAI.  A cohort of adult patients with schizophrenia was recruited from 177 psychiatric hospitals across France and observed naturalistically over 12 months. A 3-month granularity was used for treatment characterization.  The relative rate of hospitalization was assessed using a Poisson multiple regression model for auto-correlated data (SAS-GENMOD). Results were adjusted with propensity scores using potential confounders of R-LAI use vs. non-use, including history of hospitalization, severity of schizophrenia, and patterns of antipsychotic use. RESULTS: The cohort consisted of 1859 patients with 454 person years of R-LAI use, and 1306 person years of R-LAI non-use. R-LAI use was associated with an adjusted rate ratio of hospitalization of 0.66 (95% CI: 0.46 -0.96) when compared to non-use and 0.53 (95% CI: 0.32 -0.88) when compared to typical LAI antipsychotics. This was found to be associated with better compliance in patients with a history of recurrent hospitalization, and therefore compensated for the costs of treatment. CONCLUSIONS: A cohort with dynamic-exposure methodology established a successful risk-sharing agreement for a new treatment for schizophrenia.