BackgroundThe COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs).ObjectiveTo determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19.DesignRetrospective cohort.SettingEight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN).Target populationAdults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020.MeasurementsWe randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs.ResultsTwo hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error.LimitationsResults are limited by available documentation and do not capture communication between providers and patients.ConclusionAmong PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.