OBJECTIVE: Clinical implications of asymptomatic cases of the novel coronavirus disease 2019 (COVID-19) in nursing homes remain poorly understood. We assessed the association of symptom status and medical comorbidities on mortality and hospitalization risk associated with COVID-19 in residents across 15 nursing homes in Maryland. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 1970 residents from 15 nursing home facilities with universal COVID-19 testing in Maryland. METHODS: We used descriptive statistics to compare baseline characteristics, logistic regression to assess the association of comorbidities with COVID-19, and Cox regression to assess the association of asymptomatic and symptomatic COVID-19 with mortality and hospitalization. We assessed the association of comorbidities with mortality and hospitalization risk. Symptom status was assessed at the time of the first test. Maximum follow-up was 94 days. RESULTS: Among the 1970 residents (mean age 73.8, 57% female, 68% black), 752 (38.2%) were positive on their first test. Residents who were positive for COVID-19 and had multiple symptoms at the time of testing had the highest risk of mortality [hazard ratio (HR) 4.44, 95% confidence interval (CI) 2.97, 6.65) and hospitalization (subhazard ratio 2.38, 95% CI 1.70, 3.33), even after accounting for comorbidity burden. Cases who were asymptomatic at testing had a higher risk of mortality (HR 2.92, 95% CI 1.95, 4.35) but not hospitalization (HR 1.06, 95% CI 0.82, 1.38) compared with those who were negative for COVID-19. Of 52 SARS-CoV-2-positive residents who were asymptomatic at the time of testing and were closely monitored for 14 days at one facility, only 6 (11.6%) developed symptoms. CONCLUSIONS AND IMPLICATIONS: Asymptomatic infection with SARS-CoV-2 in the nursing home setting was associated with increased risk of death, suggesting a need for closer monitoring of these residents, particularly those with underlying cardiovascular and respiratory comorbidities.