Schizophrenia is a chronic disorder that is usually characterized by relapses alternating with periods of full or partial remission. We examined whether combined therapy with a psychosocial intervention for relapse prevention (PIRP) and risperidone administered by long-acting injection (RLAI) would be more effective in reducing relapses than RLAI with treatment-as-usual (TAU) among outpatients with schizophrenia. We conducted a prospective, controlled study over 2 years in 46 patients with schizophrenia receiving RLAI, of which 21 and 25 patients were assigned to the PIRP and TAU control groups, respectively. The 1- and 2-year relapse rates were lower and medication compliance was higher in the PIRP group than in the TAU group. Cox proportional analysis revealed that time from baseline to relapse was associated with RLAI discontinuation. These results indicate that PIRP can be effective in maintaining medication compliance, and that discontinuation of long-acting atypical antipsychotics might be predictive of the next relapse. However, these results need to be replicated in studies with larger samples.