Older individuals with chronic health conditions are at highest risk of adverse clinical outcomes from COVID-19, but there is widespread belief that risk to younger, relatively lower-risk individuals is negligible. We assessed the rate and predictors of life-threatening complications among relatively lower-risk adults hospitalized with COVID-19. Of 3766 adults hospitalized with COVID-19 to three hospitals in New York City from March to May 2020, 963 were relatively lower-risk based on absence of preexisting health conditions. Multivariable logistic regression models examined in-hospital development of life-threatening complications (major medical events, intubation, or death). Covariates included age, sex, race/ethnicity, hypertension, weight, insurance type, and area-level sociodemographic factors (poverty, crowdedness, and limited English proficiency). In individuals ≥55 years old (n = 522), 33.3% experienced a life-threatening complication, 17.4% were intubated, and 22.6% died. Among those <55 years (n = 441), 15.0% experienced a life-threatening complication, 11.1% were intubated, and 5.9% died. In multivariable analyses among those ≥55 years, age (OR 1.03 [95%CI 1.01-1.06]), male sex (OR 1.72 [95%CI 1.14-2.64]), being publicly insured (versus commercial insurance: Medicare, OR 2.02 [95%CI 1.22-3.38], Medicaid, OR 1.87 [95%CI 1.10-3.20]) and living in areas with relatively high limited English proficiency (highest versus lowest quartile: OR 3.50 [95%CI 1.74-7.13]) predicted life-threatening complications. In those <55 years, no sociodemographic factors significantly predicted life-threatening complications. A substantial proportion of relatively lower-risk patients hospitalized with COVID-19 experienced life-threatening complications and more than 1 in 20 died. Public messaging needs to effectively convey that relatively lower-risk individuals are still at risk of serious complications.