INTRODUCTION: The correct use of personal protective equipment (PPE) limits transmission of serious communicable diseases to healthcare workers, which is critically important in the era of coronavirus disease 2019 (COVID-19). However, prior studies illustrated that healthcare workers frequently err during application and removal of PPE. The goal of this study was to determine whether a simulation-based, mastery learning intervention with deliberate practice improves correct use of PPE by physicians during a simulated clinical encounter with a COVID-19 patient. METHODS: This was a pretest-posttest study performed in the emergency department at a large, academic tertiary care hospital between March 31-April 8, 2020. A total of 117 subjects participated, including 56 faculty members and 61 resident physicians. Prior to the intervention, all participants received institution-mandated education on PPE use via an online video and supplemental materials. Participants completed a pretest skills assessment using a 21-item checklist of steps to correctly don and doff PPE. Participants were expected to meet a minimum passing score (MPS) of 100%, determined by an expert panel using the Mastery Angoff and Patient Safety standard-setting techniques. Participants that met the MPS on pretest were exempt from the educational intervention. Testing occurred before and after an in-person demonstration of proper donning and doffing techniques and 20 minutes of deliberate practice. The primary outcome was a change in assessment scores of correct PPE use following our educational intervention. Secondary outcomes included differences in performance scores between faculty members and resident physicians, and differences in performance during donning vs doffing sequences. RESULTS: All participants had a mean pretest score of 73.1% (95% confidence interval [CI], 70.9-75.3%). Faculty member and resident pretest scores were similar (75.1% vs 71.3%, p = 0.082). Mean pretest doffing scores were lower than donning scores across all participants (65.8% vs 82.8%, p<0.001). Participant scores increased 26.9% (95% CI of the difference 24.7-29.1%, p<0.001) following our educational intervention resulting in all participants meeting the MPS of 100%. CONCLUSION: A mastery learning intervention with deliberate practice ensured the correct use of PPE by physician subjects in a simulated clinical encounter of a COVID-19 patient. Further study of translational outcomes is needed.