ObjectiveThe vertical one-handed chest compression (OHCC) technique has demonstrated superior compression power and chest compression depth (CCD) compared to conventional OHCC. This study aimed to determine if a rescuer's handedness influences the CCD during the vertical OHCC. MethodsThis prospective randomized crossover simulation trial included 59 medical doctors. Each performed a 2-min single-rescuer cardiopulmonary resuscitation (CPR) on a pediatric manikin using the vertical OHCC, once with the dominant hand (Test 1) and once with the non-dominant hand (Test 2). CPR parameters were recorded in real-time via sensors in the manikin, and the compression force exerted by each hand was measured using a force plate. ResultsThe mean and adequate CCD did not differ significantly between Test 1 and 2 (mean depth: 52 mm (interquartile range [IQR]: 49–57) in Test 1 vs. 52 mm (IQR: 49–57) in Test 2, P = 0.625; adequate depth: 97% (IQR: 37–100) in Test 1 vs. 92% (IQR: 51–99) in Test 2, P = 0.619). The mean compression force was significantly greater in the dominant hand compared to the non-dominant hand (23.1 kg ± 4.9 in dominant hand vs. 21.7 kg ± 4.1 in non-dominant hand, P < 0.001). Other parameters showed no significant differences between Tests 1 and 2. ConclusionsWhile vertical OHCC with a dominant hand generated greater force, the rescuer's handedness did not affect the CCD during the vertical OHCC.