The 2010 guidelines for cardiopulmonary resuscitation recommends that the chest be compressed at least 5 cm, with evidence that depths exceeding 5 cm may further aid resuscitation. The current piston-based mechanical device LUCAS 2™ is programmed to deliver a compression depth of 5 cm. We report 2 cases in which the LUCAS 2™ device failed to generate physiological surrogates of blood flow (ie, end-tidal carbon dioxide tension and aortic diastolic blood pressure) at levels indicative of effective chest compressions. A switch to manual compressions allowing greater compression depth yielded higher end-tidal carbon dioxide tension and arterial blood pressure. These cases depict limitations of the LUCAS 2™ device and the importance of guiding chest compression by physiological parameters. Consideration should be given to modifications to the LUCAS 2™, allowing rescuers to increase depth when required to optimize the hemodynamic efficacy of chest compression.