Two-rescuer cardiopulmonary resuscitation (CPR) is considered the best method for professional basic life support (BLS). However, in many prehospital cardiac arrest situations, one rescuer has to begin CPR alone while the other performs additional tasks. In theory, over-the-head CPR is a suitable alternative in this situation, with the added benefit of allowing the single rescuer to use a self-inflating bag for ventilation. In this trial, we compared standard single-rescuer CPR with over-the-head CPR in manikins. We planned this study using a crossover study design where each participant administered both CPR techniques in a randomized order. Ventilation and chest compression data were collected with analysis software during a 2-min CPR test for each technique. Sixty-seven emergency medical technician students participated in this trial. Over-the-head CPR allowed for superior ventilation compared to standard CPR (number of correct ventilations: 330 of 760 versus 279 of 779; P = 0.002). The quality of delivered chest compressions did not differ between the two groups (correct chest compressions: 4293 of 6304 versus 4313 of 6395; P = 0.44). In conclusion, our study has shown that over-the-head CPR may be an effective alternative BLS technique when a single professional rescuer has to perform CPR, likely offering superior ventilation and comparable chest compression quality compared with standard BLS.