OBJECTIVES: Poor adherence to antipsychotics in schizophrenia is common and associated with increased hospitalization risk, a key driver of increased costs of care. The objective was to evaluate the effectiveness of a patient-assisted medication adherence program (PAMAP) on psychiatric hospitalization rates among schizophrenia patients treated with long-acting injectable risperidone (RLAI). METHODS: Between 2009-2010, patients aged 18-65 years meeting DSM-IV criteria for schizophrenia and treated with RLAI were recruited from 36 centers in France and followed for 1 year. The PAMAP consisted of calling patients 48 hours prior their scheduled RLAI injections and within 3 days of a missed appointment. Adherent centers applied PAMAP to ≥50% of injections. Adherent patients received ≥ 80% of their injections within 5 days of the scheduled date. Otherwise, patients and centers were non-adherent. Poisson regression was used to derive rate ratios (RR) comparing psychiatric hospitalization rates among adherent and non-adherent patients and centers. Propensity scores were used to derive adjusted RRs. RESULTS: Of 506 recruited patients, 95.7% were followed up to 1 year (average age: 38.7; 64.6% males; 60.4% hospitalized in the previous year). Overall hospitalization rate over follow-up was 32.5 per 100 person-years. Fifteen centers treating 243 patients and 21 centers treating 263 patients were adherent and non-adherent, respectively. Lower hospitalization rates were associated with PAMAP (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent but adherence was not associated with disease severity nor with reduced hospitalization rates. The effect of PAMAP on hospitalizations rates was greater among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent patients (adjusted RR: 0.88 [95% CI: 0.51-1.53]). CONCLUSIONS: Adherence among schizophrenia patients partaking in a PAMAP for RLAI was high. PAMAP may reduce psychiatric hospitalization risk for schizophrenia patients with problems adhering to long-acting injectable antipsychotics treatment regimens.