Single-use N95 respirators are critical to protect staff and patients from airborne infections, but shortages may occur during disease outbreaks and other crisis situations. Wearing an N95 respirator for hours at a time (i.e., extended wear) or reusing a respirator several times (i.e., donning and doffing between uses) are practices used to ease shortages. The potential risks and benefits of these practices may vary greatly across locations and may evolve rapidly during a crisis. This report’s conclusions are not intended as a practice endorsement or call to action. Rather, this report is intended to provide practical guidance on the potential risks and benefits that clinical centers should consider during decision making about N95 respirator reuse or extended use.