ImportanceThe aerosol box has been used during the management of patients with COVID-19 to reduce health care practitioner (HCP) exposure during aerosol-generating medical procedures (AGMPs). Little is known about the effect of aerosol box use on HCP contamination and AGMP procedure time.ObjectiveTo investigate whether use of an aerosol box during AGMPs reduces HCP contamination or influences the time to successful completion and first-pass success rate for endotracheal intubation (ETI) and laryngeal mask airway (LMA) insertion.Design, Setting, and ParticipantsThis multicenter, simulation-based, randomized clinical trial was conducted from May to December 2021 at tertiary care pediatric hospitals. Participant teams performed 3 simulated patient scenarios: bag-valve-mask ventilation, ETI, and LMA insertion. During the scenarios, aerosols were generated using Glo Germ. Teams of 2 HCPs were randomly assigned to control (no aerosol box) or intervention groups (aerosol box). Statistical analysis was performed from July 2022 to February 2023.InterventionsThe aerosol box (or SplashGuard CG) is a transparent, plastic barrier covering the patient’s head and shoulders with access ports allowing HCPs to manage the airway.Main Outcomes and MeasuresThe primary outcome was surface area of contamination (AOC) on participants. Secondary outcomes were time to successful completion and first-pass success rates for ETI and LMA insertion.ResultsA total of 64 teams (128 participants) were enrolled, with data from 61 teams (122 participants) analyzed. Among the 122 participants analyzed, 79 (64.8%) were female and 85 (69.7%) were physicians. Use of an aerosol box was associated with a 77.5% overall decreased AOC to the torso (95% CI, −86.3% to −62.9%; P < .001) and a 60.7% overall decreased AOC to the facial area (95% CI, −75.2% to −37.8%; P < .001) in airway HCPs. There was no statistically significant difference in surface contamination after doffing personal protective equipment between groups. Time to completing ETI was longer in the aerosol box group compared with the control group (mean difference: 10.2 seconds; 95% CI, 0.2 to 20.2 seconds; P = .04), but there was no difference between groups for LMA insertion (mean difference: 2.4 seconds; 95% CI, −8.7 to 13.5 seconds; P = .67).Conclusions and RelevanceIn this randomized clinical trial of aerosol box use in AGMPs, use of an aerosol box reduced contamination deposition on HCPs’ torso and face predoffing; the use of an aerosol box delayed time to successful intubation. These results suggest that the incremental benefits of reduced surface contamination from aerosol box use should be weighed against delayed time to complete intubation, which may negatively affect patient outcome.Trial RegistrationClinicalTrials.gov Identifier: NCT04880668