A non-invasive method for the estimation of cardiac output in mechanically ventilated patients is described. The method is based on prolonged expiration, and relies on measurement of gas concentrations and flow rate. A pneumatic system, with an ad hoc designed orifice resistance, has been made and experimentally characterized to adapt the breathing circuit to this application. Cardiac output is calculated using two algorithms and the results are compared with the ones obtained by thermodilution. To this purpose, we prospectively enrolled twenty mechanically ventilated patients, who had undergone cardiac surgery, and both algorithms show good correlation with thermodilution (R > 0.8). The application of the first algorithm gave mean cardiac output values slightly lower than those obtained by thermodilution (-6%), while the application of the second algorithm gave higher values (+30%). Difference standard deviations between paired measurements is 0.72 L min(-1) for the first algorithm and 1.07 L min(-1) for the second one. Standard deviation obtained by the application of the first algorithm is slightly lower than those relative to other minimally invasive techniques. Through prolonged expiration, and standardization and automation of the procedure on mechanically ventilated patients, the proposed system allows to obtain a non-invasive estimation of cardiac output.