Background: Kaposi sarcoma (KS) is a type of soft tissue sarcoma due to infection with human herpes virus 8 (HHV-8) and can be associated with acquired immunodeficiency syndrome [AIDS]. Recent national population data are scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with KS in the United States (U.S). Methods: Data were abstracted from the National Inpatient Sample (NIS) Database. This database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with KS were obtained by searching for hospitalizations that contained ICD-10 code “C46” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of KS discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for KS. Patients were mainly males (91%), black (40%), mean age of 48 years, inpatient mortality of 9.3%, mean LOS of 9 days, and mean total hospital charge of 132,476 U.S dollars. The 5 most common reasons for hospitalization by ICD 10 code categories were infections (52.4%), cardiovascular (6.5%), respiratory (6.1%), neoplasm and hematologic (5.6%), and skin (5.6%). The 5 most common specific principal diagnoses for hospitalizations were Human immunodeficiency virus [HIV] disease (29.1%), sepsis (12.7%), left leg cellulitis (2.7%), pneumonia (2.2%), and Acute kidney injury (1.8%). Conclusions: Hospitalizations for KS patients are mostly black middle-aged men, with high inpatient mortality, long LOS, and significant hospital charges. Infections and HIV were the most common reasons for hospitalizations. Management of underlying HIV and measures for prevention, early detection, and prompt treatment of infections in the outpatient setting are important in preventing hospitalizations of these patients.