OBJECTIVES: Few studies have compared diabetes-related hospitalization and peripheral lower-extremity diseases-related hospitalization using the same data source. This study examines the epidemiology and economic costs of diabetes-related hospitalization and peripheral lower-extremity diseases-related hospitalization from a national database.  METHODS: A retrospective analysis of the 2012 National Inpatient Sample (NIS). Diabetes-related hospitalization was defined by discharge records with principal or secondary diagnosis of Diabetes (250.XX). Peripheral lower-extremity disease (PLE) was defined using diagnosis codes for peripheral arterial diseases or neuropathy; PLE-related hospitalization was defined by discharge records with principal or secondary diagnosis of peripheral lower-extremity diseases. Diabetes comorbidity for PLE-related hospitalization was defined by any diagnosis that included a code for diabetes. Descriptive analysis was used to explore epidemiology of diabetes-related hospitalization and PLE-related hospitalization. Generalized linear model was used for examining the costs of diabetes-related hospitalization and PLE hospitalization. RESULTS: