The development of postoperative organ failures severely affects the prognosis of surgical patients, and substantially increases the utilization of resources and the costs of care. The presence of tissue hypoxia is particularly common and likely results from an impairment of the adaptive mechanisms of myocardial function, leading to an inappropriately low cardiac output and from the effects of inflammatory mediators. Importantly, tissue hypoxia can be detected early. Indeed, hypoxic tissues will compensate the hypoperfusion by increasing oxygen extraction (O2ER) over a threshold value, a change that will also be reflected by a decreased venous oxygen saturation, and if uncompensated by lactic acidosis. Hence, the use of oxygen extraction calculated from arterial and central venous oxygen saturation as a therapeutic goal is appropriate to monitor goal-directed hemodynamic strategies, as it reflects the balance between oxygen delivery and consumption. In place of O2ER or its surrogate, mixed venous oxygen saturation, the use of oxygen-derived values measured in central blood drawn from the routinely placed central line, in place of pulmonary artery catheter, may represent a valuable alternative. Indeed, recent evidence suggests that a multifaceted goal-directed strategy, including fluid challenge, blood transfusion and inotropes titrated to keep central venous oxygen saturation higher than a predetermined threshold of 70% was associated with decreased mortality and rate of organ failures when applied from the early phase of septic shock or severe sepsis. The aim of the present multicentre prospective randomized study was to compare the outcomes of patients randomized to a conventional management or to a therapeutic strategy guided by O2ER estimate (O2ERe) calculated from the arterial oxygen saturation and the central venous saturation ScvO2. Specifically, we hypothesized that the use of a goal-directed protocol aimed at maintaining the O2ERe below a previously defined “critical” (able to discriminate survivors from non-survivors) value of 26.7% during surgical interventions in high-risk patients will reduce the rate of postoperative organ failures, hospital length of stay and mortality, as compared with the standard management based on the monitoring of mean arterial pressure, central venous pressure and urine output.