Background: Penile cancer (PC) is a rare malignancy that is more common in developing countries. However, recent studies have shown rising incidence-based mortality in the United States (U.S). National population data is scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with PC. Methods: Data were abstracted from the National Inpatient Sample (NIS) 2020 Database. T≥his 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 PC were obtained by searching for hospitalizations that contained the International Classification of Diseases (ICD)-10 code “C60” 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 PC 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 PC. Patients were predominantly white (65.9%), mean age of 66.5 years, inpatient mortality of 4.7%, mean LOS of 6.1 days, and mean total hospital charge of 71,447 U.S dollars. The 7 most common reasons for hospitalization by ICD 10 code categories were neoplasm and hematological (35.9%), nonspecific (17.3%), infections (12.6%), injury & poisoning (7.1%), cardiovascular (6.4%), and Genito-urinary (4.3%). The 5 most common specific principal diagnoses for hospitalizations were malignant neoplasm of the penis (29.1%), admission for chemotherapy (12.7%), sepsis (2.7%), Malignant neoplasm of the glans penis (2.2%), secondary neoplasm of inguinal and lower limb nodes (1.8%). Conclusions: Hospitalized PC patients are mostly elderly white men. Infections, chemotherapy, and PC were the most common reasons for hospitalizations. Optimal management of underlying malignancy, prevention, and prompt treatment of infections in the outpatient is important in reducing hospitalizations of these patients.