High-rise buildings present unique challenges to providing high-quality CPR. We investigated the effect of using a mechanical compressor and supraglottic airway on flow time and CPR quality in simulated cardiac arrests occurring within a high-rise building. Twelve teams of EMS providers performed CPR according to 4 scenarios: manual compression and ventilation through bag-valve-mask (MAB) or supraglottic airway (MAS); mechanical compression and ventilation through bag-valve-mask (MEB) or supraglottic airway (MES). Chest compression indices did not differ significantly among the groups. The mechanical compression groups had a higher flow time fraction from exiting the elevator until the manikin was loaded into the ambulance than the manual compression groups. The supraglottic airway groups had higher flow time fractions from entering the elevator until the end of the scenario than the bag-valve-mask groups. The total flow time fraction was lowest in the MAB group and was highest in the MEB group (P < 0.001). In simulated cardiac arrest in a high-rise building, the use of a supraglottic airway maintained flow time at a level similar to that observed with the use of a mechanical compressor. Moreover, the use of a mechanical compressor and a supraglottic airway increased the flow time most effectively.