OBJECTIVES: This real-world retrospective study aims at comparing re-hospitalization patterns and costs among patients with schizophrenia receiving paliperidone palmitate (PP) or oral antipsychotics (AP) in an inpatient setting. METHODS: Hospital discharge and billing records from the Premier Perspective Comparative Hospital Database were analyzed for adult patients who had a schizophrenia-related hospitalization with either PP or oral AP treatment (index hospitalization) between 1/2009 and 3/2012 and no evidence of prior treatment with other long-acting AP. Inverse probability of treatment weights (IPTW) based on propensity scores were used to weight cohorts in order to reduce confounding. Patients treated with PP during their index hospitalization were compared to those treated with oral AP in terms of re-hospitalizations and ER visits using the Andersen-Gill Cox extension of multivariate Cox proportional hazard models. Hospital costs (re-hospitalizations, ER, and hospital outpatient visits) of patients treated with PP were compared to those of patients treated with oral AP using a multivariate generalized linear model regression that was weighted by the combined weight of the IPTW and the observation period length. RESULTS: After applying IPTW, weighted mean age was 43.4 years for PP (N=374; N weighted=19,526) and 45.6 years for oral AP (N=45,251; N weighted=26,099) patients. The risk of all-cause re-hospitalizations or ER visits was significantly lower for the PP cohort compared to the oral AP cohort (hazard ratio [HR], [95%CI] = 0.61, [0.59;0.63] p<.0001). Similarly, hospital costs six months after index hospitalization were lower for the PP cohort compared to the oral AP cohort (adjusted mean monthly cost difference [95%CI]: - $404[-781;-148], p<.0001). CONCLUSIONS: This hospital database analysis using the IPTW method found that, compared with oral AP, PP was associated with a lower risk of an ER visit and re-hospitalization in patients with schizophrenia receiving antipsychotics in the hospital setting, resulting in lower hospital costs.