Importance: Some patients are avoiding essential care for fear of contracting coronavirus disease 2019 (COVID-19) in hospitals. There are few data, however, on the risk of acquiring COVID-19 in US hospitals. Objective: To assess the incidence of COVID-19 among patients hospitalized at a large US academic medical center in the 12 weeks after the first inpatient case was identified. Design, Setting, and Participants: This cohort study included all patients admitted to Brigham and Women's Hospital (Boston, Massachusetts) between March 7 and May 30, 2020. Follow-up occurred through June 17, 2020. Medical records for all patients who first tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction (RT-PCR) on hospital day 3 or later or within 14 days of discharge were reviewed. Exposures: A comprehensive infection control program was implemented that included dedicated COVID-19 units with airborne infection isolation rooms, personal protective equipment in accordance with US Centers for Disease Control and Prevention recommendations, personal protective equipment donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. Main Outcomes and Measures: Whether infection was community or hospital acquired based on timing of tests, clinical course, and exposures. Results: Over the 12-week period, 9149 patients (mean [SD] age, 46.1 [26.4] years; median [IQR] age, 51 years [30-67 years]; 5243 female [57.3%]) were admitted to the hospital, for whom 7394 SARS-CoV-2 RT-PCR tests were performed; 697 COVID-19 cases were confirmed, translating into 8656 days of COVID-19-related care. Twelve of the 697 hospitalized patients with COVID-19 (1.7%) first tested positive on hospital day 3 or later (median, 4 days; range, 3-15 days). Of these, only 1 case was deemed to be hospital acquired, most likely from a presymptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. Among 8370 patients with non-COVID-19-related hospitalizations discharged through June 17, 11 (0.1%) tested positive within 14 days (median time to diagnosis, 6 days; range, 1-14 days). Only 1 case was deemed likely to be hospital acquired, albeit with no known exposures. Conclusions and Relevance: In this cohort study of patients in a large academic medical center with rigorous infection control measures, nosocomial COVID-19 was rare during the height of the pandemic in the region. These findings may inform practices in other institutions and provide reassurance to patients concerned about contracting COVID-19 in hospitals.