Massive pulmonary embolism (PE) is a life-threatening condition that mandates urgent pulmonary reperfusion. To adequately monitor hemodynamic of these highly unstable patients remains challenging because there is no validated correlation between the arterial oxygen level, the severity of the PE, and the efficacy of the adopted reperfusion therapy. We report on 2 patients presenting with massive PE, who were monitored measuring simultaneously the cardiac output and the pressure gradient between arterial and end-tidal CO2. The P(a-ET CO2) has timely suggested the efficacy of the attempted reperfusion treatment. This easily obtainable physiologic gradient provides immediate information on pulmonary blood flow states as well as on ventilatory functions. This noninvasive bedside parameter should be part of the monitoring of mechanically ventilated patients treated for massive PE.