Objectives: Surgical masks and N95 filtering facepiece respirators (FFRs) prevent the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and protect medical personnel. Increased demands for surgical masks and N95 FFRs during the coronavirus disease 2019 (COVID-19) pandemic has resulted in the shortage crisis. However, there is no standard protocol for safe reuse of the N95 FFRs. In this systematic review, we aimed to evaluate the effectiveness of existing decontamination methods of surgical masks and N95 FFRs and provide evidence-based recommendations for selecting an appropriate decontamination method.Methods: We performed systematic searches of Ovid MEDLINE and Ovid EMBASE electronic databases. The last search was performed April 11, 2020. Any trials studying surgical masks and/or N95 FFRs decontamination were included. Outcomes were disinfections of virus and bacteria, restoration of the filtration efficiency, and maintenance of the physical structure of the mask.Results: Overall, 15 studies and 14 decontamination methods were identified. A low level of evidence supported 4 decontamination methods: ultraviolet (UV) germicidal irradiation (9 studies), moist heat (5 studies), microwave-generated steam (4 studies), and hydrogen peroxide vapor (4 studies). Therefore, we recommended these 4 methods, and we recommended against use were given for the other 10 methods.Conclusions: A low level of evidence supported the use of UV germicidal irradiation, moist heat, microwave-generated steam, and hydrogen peroxide vapor for decontamination and reuse of N95 FFRs. These decontamination methods were effective for viral and bacterial disinfection as well as restoration of the filtration efficiency, and the physical structure of the FFRs.