OBJECTIVES: This study aimed to determine whether personal protective equipment (PPE) results in deterioration in chest compression (CC) quality and greater fatigue for administering health care providers (HCPs). METHODS: In this multicenter study, HCPs completed 2 sessions. In session 1 (baseline), HCPs wore normal attire; in session 2, HCPs donned full PPE. During each session, they performed 5 minutes of uninterrupted CCs on a child manikin. Chest compression rate, depth, and release velocity were reported in ten 30-second epochs. Change in CC parameters and self-reported fatigue were measured between the start and 2- and 5-minute epochs. RESULTS: We enrolled 108 HCPs (prehospital and in-hospital providers). The median CC rate did not change significantly between epochs 1 and 10 during baseline sessions. Median CC depth and release velocity decreased for 5 minutes with PPE. There were no significant differences in CC parameters between baseline and PPE sessions in any provider group. Median fatigue scores during baseline sessions were 2 (at start), 4 (at 2 minutes), and 6 (at 5 minutes). There was a significantly higher median fatigue score between 0 and 5 minutes in both study sessions and in all groups. Fatigue scores were significantly higher for providers wearing PPE compared with baseline specifically among prehospital providers. CONCLUSIONS: During a clinically appropriate 2-minute period, neither CC quality nor self-reported fatigue worsened to a significant degree in providers wearing PPE. Our data suggest that Pediatric Basic Life Support recommendations for CC providers to switch every 2 minutes need not be altered with PPE use.