High-quality chest compression (CC) is the crux of survival for cardiac arrest patients. While, rescuers' position setting relative to patients during CC was unrecommended in the present guidelines. We aimed to assess the impact of position settings on CC quality during cardiopulmonary resuscitation (CPR) and to test the heterogeneity related to rescuers' characteristics. We conducted randomized, crossover, simulation trials with clinical students unfamiliar with CPR. The participants received standard training on performing CC and were divided randomly into two groups. The two groups separately performed CC with standing and kneeling positions in turn, forming the crossover design. The trials were performed with standard manikin models. CC quality indicator data were recorded by the tracking and feedback system automatically. 156 participants finished at least one round of trial, with 126 participants finishing both rounds. Records for CC with kneeling and standing positions showed statistically significant differences in the correct rate, pause happening, average depth, and happening of over-depth compression. Regression analysis also implied that larger compression depths with the standing position were related to larger height and BMI of the participants. When performing CC, the standing position will lead to lower CC quality by larger chance of pause happening and over-depth compression. In addition, compression depth gaps between CC with kneeling and standing position were related with rescuer characteristics including height and BMI, with a threshold effect.