AbstractBackground:Healthcare personnel (HCP) may encounter unfamiliar personal protective equipment (PPE) during clinical duties, yet we know little about their doffing strategies in such situations.Objective:To better understand how HCP navigate encounters with unfamiliar PPE and the factors that influence their doffing strategies.Setting:The study was conducted at 2 Midwestern academic hospitals.Participants:The study included 70 HCP: 24 physicians and resident physicians, 31 nurses, 5 medical or nursing students, and 10 other staff. Among them, 20 had special isolation unit training.Methods:Participants completed 1 of 4 doffing simulation scenarios involving 3 mask designs, 2 gown designs, 2 glove designs, and a full PPE ensemble. Doffing simulations were video-recorded and reviewed with participants during think-aloud interviews. Interviews were audio-recorded and analyzed using thematic analysis.Results:Participants identified familiarity with PPE items and designs as an important factor in doffing. When encountering unfamiliar PPE, participants cited aspects of their routine practices such as designs typically used, donning and doffing frequency, and design cues, and their training as impacting their doffing strategies. Furthermore, they identified nonintuitive design and lack of training as barriers to doffing unfamiliar PPE appropriately.Conclusion:PPE designs may not be interchangeable, and their use may not be intuitive. HCP drew on routine practices, experiences with familiar PPE, and training to adapt doffing strategies for unfamiliar PPE. In doing so, HCP sometimes deviated from best practices meant to prevent self-contamination. Hospital policies and procedures should include ongoing and/or just-in-time training to ensure HCP are equipped to doff different PPE designs encountered during clinical care.