Background: Personal Protective Equipment (PPE) is required to safely work with biological agents of bacterial (i.e. Mycobacterium tuberculosis) or viral origin (Ebola and SARS). COVID-19 pandemic especially has created unforeseen public health challenges including a global shortage of PPE needed for the safety of health care workers (HCWs). Although sufficient stocks of PPE are currently available, their critical shortage may develop soon due to increase in demand and depletion of existing supply lines. To empower our HCWs and ensure their continued protection, proactive measures are urgently required to develop procedures to safely decontaminate the PPEs to allow their "selective reuse" during contingency situations. Methods: Herein, we have successfully developed a decontamination method based on vaporized hydrogen peroxide (VHP). We have used a range of concentration of hydrogen peroxide to disinfect PPE (coveralls, face-shields, and N-95 masks). To ensure a proper disinfection, we have evaluated three biological indicators namely Escherichia coli, Mycobacterium smegmatis and spores of Bacillus stearothermophilus, considered as the gold standard for disinfection processes. We next evaluated the impact of repeated VHP treatment on physical features, permeability, and fabric integrity of coveralls and N-95 masks. Next, we performed Scanning Electron Microscopy (SEM) to evaluate microscopic changes in fiber thickness of N-95 masks, melt blown layer or coverall body suits. Considering the fact that any disinfection procedure should be able to meet local requirements, our study included various regionally procured N-95 masks and coveralls available at our institute All India Institute of Medical Sciences (AIIMS), New Delhi, India. Lastly, the practical utility of VHP method developed herein was ascertained by operationalizing a dedicated research facility disinfecting used PPE during COVID-19. Results: Our prototype studies show that a single VHP cycle (7-8% Hydrogen peroxide) could disinfect PPE and PPE housing room of about 1200 cubic feet (length10 ft × breadth 10 ft × height 12 ft) in less than 10 min, as noted by a complete loss of B. stearothermophilus spore revival. The results are consistent and reproducible as tested in over 10 cycles in our settings. Further, repeated VHP treatment did not result in any physical tear, deformity or other appreciable change in the coverall and N-95 masks. Our permeation tests evaluating droplet penetration did not reveal any change in permeability post-VHP treatments. Also, SEM analysis indeed revealed no significant change in fiber thickness or damage to fibers of coveralls or melt blown layer of N-95 masks essential for filtration. There was no change in user comfort and experience following VHP treatment of PPE. Based on results of these studies, and parameters developed and optimized, an institutional research facility to disinfect COVID-19 PPE is successfully established and operationalized with more than 80% recovery rate for used PPE post-disinfection. Conclusions: Our study, therefore, successfully establishes the utility of VHP to effectively disinfect PPE for a possible reuse as per the requirements. VHP treatment did not damage coveralls, cause physical deformity and also did not alter fabric architecture of melt blown layer. We observed that disinfection process was successful consistently and therefore believe that the VHP-based decontamination model will have a universal applicability and utility. This proces2s can be easily and economically scaled up and can be instrumental in easing global PPE shortages in any biosafety facility or in health care settings during pandemic situation such as COVID-19.