question: Objectives: To evaluate reinfection rates and protective effectiveness of prior disease among patients with coronavirus disease 2019 (COVID-19) infection in the United States. Design Retrospective cohort study Setting: One multi-hospital health system in Ohio and Florida Participants: All 150,325 patients who were tested for COVID-19 infection via PCR from March 12, 2020 to August 30, 2020. Testing performed up to January 7, 2021 in these patients was included for analysis. Healthcare workers were excluded. Main outcome measures The main outcome was reinfection, defined as infection [≥] 90 days after initial testing. Secondary outcomes were symptomatic infection and protective effectiveness of prior infection. Results: Of 150,325 patients tested for COVID-19 prior to August 30, 8,845 (5.9%) tested positive and 141,480 (94.1%) tested negative. 974 (11%) of the positive patients were retested after 90 days, and 56 had possible reinfection. Of those, 26 (46.4 %) were symptomatic. Of those with initial negative testing, 4,163 (12.9%) were subsequently positive and 2,460 of those (59.1%) were symptomatic. Protective effectiveness of prior infection was 78.5% (95% confidence interval 72.0 to 83.5), and against symptomatic infection was 83.1% (95% confidence interval 75.1 to 88.5). Protective effectiveness increased over time. Conclusions: Prior infection in patients with COVID-19 was highly protective against reinfection and symptomatic disease. Protective effectiveness increased over time, suggesting that viral shedding or ongoing immune response may persist beyond 90 days and may not represent true reinfection. As vaccine supply is a limited resource around the world, patients with known history of COVID-19 could delay early vaccination to allow for the most vulnerable to access the vaccine and slow transmission.