Risperidone is the first of the second-generation antipsychotics available in a long-acting injectable form (RLAI). This form of delivery has proven efficacy and safety in the treatment of schizophrenia. However, outcome studies in ‘real-world’ clinical samples are lacking. We carried out a retrospective study using a computerized repository of clinical data from eight Veterans Affairs Medical Centers. Compliance with outpatient medication and metabolic monitoring frequency was evaluated in schizophrenia spectrum patients during treatment with oral risperidone (RispPO) and after switch to RLAI. Propensity scores were computed during baseline when both groups were on RispPO, and the two groups were matched on propensity scores. Matching on propensity score was successful: 132 RispPO patients were well matchedto 132 RLAI patients during the RispPO Baseline Period. Days until medication discontinuation were longer in the RLAI group (679.2±499.3) than the RispPO group (403.7±365.1, P<0.0001). Days late for receiving medication were significantly shorter during the RLAI treatment (5.6±6.2) than the RispPO treatment (8.2±8.6, P<0.004). Metabolic monitoring frequency was significantly greater for patients switched to RLAI for patients maintained on RispPO treatment. Outpatient medication compliance is enhanced during treatment with RLAI compared with treatment with RispPO, as is the rate of monitoring for metabolic measures.