Background: Identification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care. Objective: To examine if age TRANS, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations. Design: Cross-sectional. Setting: 70 counties within 12 states participating in the Coronavirus Disease MESHD 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults TRANS residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System. Participants: U.S. community-dwelling adults TRANS ([≥]18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020. Measurements: Adjusted rate ratios (aRR) of hospitalization by age TRANS, sex, race/ethnicity and underlying medical conditions ( hypertension MESHD hypertension HP, coronary artery disease MESHD, history of stroke MESHD stroke HP, diabetes, obesity MESHD obesity HP [BMI [≥]30 kg/m2], severe obesity MESHD obesity HP [BMI[≥]40 kg/m2], chronic kidney disease HP kidney disease MESHD, asthma MESHD asthma HP, and chronic obstructive pulmonary disease MESHD chronic obstructive pulmonary disease HP). Results: Our sample included 5,416 adults TRANS with COVID-19-associated hospitalizations. Adults TRANS with (versus without) severe obesity MESHD obesity HP (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease HP kidney disease MESHD (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity MESHD obesity HP (aRR:2.9; 95%CI: 2.3, 3.5), hypertension MESHD hypertension HP (aRR:2.8; 95%CI: 2.3, 3.4), and asthma MESHD asthma HP (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age TRANS, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults TRANS [≥]65 years, 45-64 years (versus 18-44 years), males TRANS (versus females TRANS), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites). Limitations: Interim analysis limited to hospitalizations with underlying medical condition data. Conclusion: Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.