OBJECTIVES: Describe changes in Clinical Global Impressions Severity (CGI-S) scores for adults with schizophrenia and/or schizoaffective disorder recently initiated on a new oral atypical antipsychotic (OA) or paliperidone palmitate (PP). METHODS: Adults with schizophrenia and/or schizoaffective disorder captured in the Duke Mindlinc EMR system (1/1/2010- 12/31/2011), with >90 days of treatment with the index therapy (first PP or OA prescription following a switch), CGI-S score at baseline, 1 or more CGI-S scores over 90 days post-index, and data activity 180 days prior to and 270 days post-index (proxy for eligibility). CGI-S scores were evaluated in two 90-day windows prior to and three 90-day windows post-index date. Changes in CGI-S over time were assessed using Cochran-Mantel-Haenszel tests and generalized estimating equation models. RESULTS: A total of 980 patients (63 PP/917 OA) met all criteria. Patients were of similar mean age (PP 41+SD 11.5; OA 39+11.6; p=0.2011) and gender (female: PP 48%; OA 49%; p=0.8626).  PP patients showed significantly greater CGI-S at baseline (PP 4.8+1.0); OA 4.3+1.1; p=0.0011), more comorbidities, and a higher percentage hospitalized 180 days prior to index (PP 22%; OA 11%; p=0.0075). While changes in CGI-S over time (Time -2, Time -1, Baseline, Time 1, Time 2, and Time 3) were modest, CGI-S Scores for PP patients (PP- 4.5+1.4, 4.6+1.5, 4.8+1.0, 4.6+1.0, 4.4+1.1, 4.2+1.3) showed greater improvement over time versus OA patients (OA- 4.1+1.2, 4.2+1.2, 4.3+1.1, 4.1+1.1, 4.2+1.1, 4.1+1.2).  CONCLUSIONS: In this ‘real-world’ evaluation of CGI-S scores using EMR data, PP patients showed an improvement over time while OA patients remained relatively flat.