BACKGROUND: Personal protective equipment doffing protocols can reduce risks of pathogen self-contamination. Powered air-purifying respirators may increase these risks. This study compares viral contamination and errors during simulated doffing of single-layer versus double-layer hood powered air-purifying respirators. METHODS: Eight participants performed 2 simulations (video recorded for failure modes [FMs] and effects analysis): 1 single-layer hood (laid over Tyvek suit) and 1 double-layer hood (top laid over and bottom tucked into suit). Hoods were contaminated with viruses. After doffing, inner gloves, face, hands, and scrubs were sampled. RESULTS: Virus contaminated at least 1 site in 6/8 single- and 5/8 double-layer simulations. Virus-contaminated inner gloves in single- (6 participants, median 5.42 × 10 DISCUSSION: Double-layer doffing reduced inner glove contamination. The double-layer protocol may reduce glove-face shield contact but allow more opportunities for error. Double-layer doffing errors may less frequently lead to contamination than single layer. CONCLUSIONS: Contamination and FMs may differ between double- and single-layer doffing. Although inner glove contamination was reduced, double-layer doffing may need redesign to reduce FMs and contamination.