OBJECTIVES: In order to examine comparative research questions using data from a naturalistic, observational study (REACH-OUT) of adult patients with schizophrenia, non-traditional methods were needed.  This abstract  describes the use of multiple control groups to maximize inclusion of paliperidone palmitate (PP) patients in REACH-OUT who would otherwise be excluded from analysis due to poor propensity score matching with registry controls (patients receiving oral atypical antipsychotics (OAT)). The matched cohorts (PP and combined OAT) will be used in future resource use comparisons. METHODS: Because matching on propensity of PP treatment did not yield an adequate number of matched registry controls, a secondary set of OAT controls was extracted from MarketScan® claims data. PP patients unmatched to registry controls were matched to claims controls using a 1:1 propensity score matching. Post-match baseline characteristics for the PP and combined OAT cohort were examined using descriptive statistics. Outcomes from the claims-based control group will be adjusted for source bias based on 500 simulations, according to the Stuart-Rubin (S-R) methodology. RESULTS: Out of 354 PP with non-missing baseline data, 190 were matched to registry controls and the remaining 164 were matched to the supplemental control group.  The final matched PP and OAT cohorts were balanced in observed attributes such as age (41.4 years vs. 42.0, p=0.552), gender distribution (70.3% vs. 65.5% male, p=0.171), ≥1 baseline hospitalization (29.7% vs. 34.5%, p=0.171), and ≥1 baseline ER visit (31.1% vs. 35.6%, P=0.202), respectively.  Initial S-R simulations suggest outcomes for the supplemented control group are similar to the cohort of all REACH-OUT controls (e.g., 6 month admission rates, 18.9% and 22.6%, respectively). CONCLUSIONS: Use of multiple control groups permitted successful propensity score matching of all registry PP patients allowing for greater power, better precision, and increased external validity in the forthcoming analysis of the treatment effect of PP.