OBJECTIVES: Lack in treatment adherence in schizophrenia often leads to an increase of relapses and, consequentially, to an increase for direct health care costs (eg, hospitalizations). The aim of the SMART study (Schizophrenia Medications Adherence: long-acting Risperidone versus other Therapies) is to assess the variation in total health-related costs among schizophrenic patients switching from oral antipsychotics to Long Acting Injectable Risperidone (LAI-R). METHODS: A multicenter, retrospective observational cohort study based on Local Health Units administrative databases was conducted. Patients with a diagnosis of Schizophrenia, schizotypal and delusional disorders, with a first prescription of LAI-R between January 1, 2007 and December 31, 2008 and a previous treatment with oral antipsychotics were enrolled. Direct medical costs (drugs, hospitalizations, Department of Mental Health services, outpatient specialist services) were evaluated during the 12 months preceding and following the date of inclusion. RESULTS: A total of 116 patients were enrolled, 57 male and 59 female, aged 49±17 years old. Total average disease-related cost per patient was €5.003,49 during the period preceding LAI-R and €4.138,62 during the LAI-R period (-€864,88, -17%, p=0.021). The cost increase for antipsychotic drugs (from €291.41 to €2445.94, p<0.001) was offset by a cost reduction for semi-residentiality (from €276.69 to €23.78, p=0.884), residentiality (from €2,669.90 to €831.52, p=0.004), Department of Mental Health services (from €77.25 to €479.88, p<0.001) and hospitalizations (from €1723.67 to €772.61, p=0.005); we registered a decrease in mean length of stay (LOS) (from 4.1 days to 1.2, p=0.002) and in the number of hospitalizations per patient (from 0.27 to 0.08, p<0.001); 24% patients were hospitalized during the period preceding LAI-R and 8% during the LAI-R period. Moreover, the cost for services not related to schizophrenia showed a slight reduction (from €1318.78 to €1016.62, p=0.417). CONCLUSIONS: This therapeutic strategy appears to be cost saving, especially with regard to the reduction in hospitalizations.