OBJECTIVE After cardiac surgery, functional residual capacity (FRC) after extubation is reduced significantly. We hypothesized that ventilation according to the open lung concept (OLC) attenuates FRC reduction after extubation. DESIGN A prospective, single-center, randomized, controlled clinical study. SETTING Cardiothoracic operating room and intensive care unit of a university hospital. PATIENTS Sixty-nine patients scheduled for elective coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass. INTERVENTIONS Before surgery, patients were randomly assigned to three groups: (1) conventional ventilation (CV); (2) OLC, started after arrival in the intensive care unit (late open lung); and (3) OLC, started directly after intubation (early open lung). In both OLC groups, recruitment maneuvers were applied until Pao2/Fio2 was >375 Torr (50 kPa). No recruitment maneuvers were applied in the CV group. MEASUREMENTS AND MAIN RESULTS FRC was measured preoperatively and 1, 3, and 5 days after extubation. Peripheral hemoglobin saturation (Spo2) was measured daily till the third day after extubation while the patient was breathing room air. Hypoxemia was defined by an Spo2 value < or =90%. Averaged over the 5 postoperative days, FRC was significantly higher in the early open lung group and tended to be higher in the late open lung group, in comparison with the CV group (mean +/- sem: CV, 1.8 +/- 0.1; late open lung,1.9 +/- 0.1; and early open lung, 2.2 +/- 0.1l). In the CV group, 37% of the patients were hypoxic on the third day after extubation, compared with none of the patients in both OLC groups. CONCLUSIONS After cardiac surgery, earlier application of OLC resulted in a significantly higher FRC and fewer episodes of hypoxemia than with CV after extubation.