OBJECTIVES: To evaluate the impact of metabolic comorbidities on healthcare resource utilization and costs in hospitalized patients with schizophrenia. METHODS: A retrospective observational study was conducted utilizing data from the Premier Perspective Database™ from October 1, 2010 to May 31, 2012. Patients with an admitting primary or secondary diagnosis of schizophrenia during the study period were eligible for inclusion. Patients were classified as having 0, 1, 2, or 3+ metabolic comorbidities based upon diagnoses of diabetes mellitus, hyperglycemia, hypertension, dyslipidemia, coronary heart disease, ischemic heart disease, or cardiovascular disease (CVD) during their index hospitalization. Generalized linear models were used to compare costs across the 4 comorbidity cohorts (0, 1, 2, 3+). Logistic regressions were used to compare the likelihood of readmission and the likelihood of death among the comorbidity cohorts. RESULTS: A total of 57,506 patients met all inclusion criteria; 33.9% with 0 comorbidities, 26.7% with 1 comorbidity, 19.9% with 2 comorbidities, and 19.4% with 3 or more comorbidities. Among patients with comorbidities, 57% had hypertension, 28% had diabetes, 30% had hyperlipidemia, 10% had coronary/ischemic heart disease, 4% had CVD, and 2% had hyperglycemia. As the number of comorbidities increased from 0 to 3+, there were increases in medical costs ($9,619 to $13,111; P<0.0001), pharmacy costs ($501 to $1,540; P<0.0001), and total costs ($10,120 to $14,651; P<0.0001). Patients with a higher number of comorbidities were more likely to have a readmission for any cause (9% to 13%; P<0.0001) and die during their index hospitalization (0.3% to 2%; P<0.0727), although increases in mortality were not statistically significant. CONCLUSIONS: A high prevalence of metabolic comorbidities was found in this study population of hospitalized schizophrenia patients. An increase in the number of metabolic comorbidities had adverse clinical and economic consequences, including increased costs and readmission rates.