The aim of this systematic review is to evaluate the impact of personal protective equipment (PPE) on medical device use during public health emergency responses. We conducted a systematic literature search of peer-reviewed journals in PubMed, Web of Science, and EBSCO databases. Twenty-nine of 92 articles published between 1984 and 2015 met the inclusion criteria for the review. Although many medical device use impacts were reported, they predominantly fell into 3 categories: airway management, drug administration, and diagnostics and monitoring. Chemical, biological, radiological, and nuclear (CBRN)-PPE increased completion times for emergency clinical procedures by as much as 130% and first attempt failure rates by 35% (anesthetist) versus 55% (non-anesthetist). Effects of CBRN-PPE use depend on device, CBRN-PPE level, and clinician experience and training. Continuous clinical training of responders in CBRN-PPE and device modifications can improve safety and effectiveness of medical device use during public health emergency response.