Background: During the 2014-2016 Ebola virus epidemic, more than 500 health care workers (HCWs) died in spite of the use of personal protective equipment (PPE). The Johns Hopkins University Center for Bioengineering Innovation and Design (CBID) and Jhpiego, an international nongovernmental organization affiliate of Johns Hopkins, collaborated to create new PPE to improve the ease of the doffing process. Methods: HCWs in Liberia and a US biocontainment unit compared standard M edecins Sans Fronti ere PPE (PPE A) with the new PPE (PPE B). Participants wore each PPE ensemble while performing simulated patient care activities. Range of motion, time to doff, comfort, and perceived risk were measured. Results: Overall, 100% of participants preferred PPE B over PPE A (P < .0001); 98.1% of respondents would recommend PPE B for their home clinical unit (P < .0001). There was a trend towards greater comfort in PPE B. HCWs at both sites felt more at risk in PPE A than PPE B (71.9% vs 25% in Liberia, P < .0001; 100% vs 40% in the US biocontainment unit, P < .0001). Conclusions: HCWs preferred a new PPE ensemble to M edecins Sans Fronti ere PPE for high-consequence pathogens. Further studies on the safety of this new PPE need to be conducted.