Background The effect of mechanical CPR is diversely described in the literature. Different mechanical CPR devices are available. The corpuls cpr is a new generation of piston-driven devices and was launched in 2015. The COMPRESS-trial analyzes quality of chest compression and CPR-related injuries in cases of mechanical CPR by the corpuls cpr and manual CPR. Methods This article describes the design and study protocol of the COMPRESS-trial. This observational multi-center study includes all patients who suffered an out-of-hospital cardiac arrest (OHCA) where CPR is attempted in four German emergency medical systems (EMS) between January 2020 and December 2022. EMS treatment, in-hospital-treatment and outcome are anonymously reported to the German Resuscitation Registry (GRR). This information is linked with data from the defibrillator, the feedback system and the mechanical CPR device for a complete dataset. Primary endpoint is chest compression quality (complete release, compression rate, compression depth, chest compression fraction, CPR-related injuries). Secondary endpoint is survival (return of spontaneous circulation (ROSC), admission to hospital and survival to hospital discharge). The trial is sponsored by GS Elektromedizinische Geräte G. Stemple GmbH. Discussion This observational multi-center study will contribute to the evaluation of mechanical chest compression devices and to the efficacy and safety of the corpuls cpr. Trial registration DRKS, DRKS-ID DRKS00020819. Registered 31 July 2020.