The aim of this study was to evaluate the concept that tissue oxygen debt reflected by inadequate oxygen consumption (VO2) in the intraoperative and immediate postoperative periods is a common determinant of multisystem organ failure and death. We measured the cumulative tissue oxygen debt during and immediately after 100 consecutive high-risk surgical operations in 98 patients and correlated these data with the subsequent development of lethal and nonlethal organ failure complications. The tissue VO2 deficit was calculated as the measured VO2 minus the estimated VO2 requirements corrected for both temperature and anesthesia; the net cumulative VO2 deficit was calculated as the integrated area under the VO2 deficit-time curve. The maximum cumulative VO2 deficit averaged 33.5 +/- 36.9 (SD) L/m2 in nonsurvivors, 26.8 +/- 32.1 L/m2 in survivors with organ failure, and 8.0 +/- 10.9 L/m2 in survivors without organ failure. The time postoperatively to reach the maximal cumulative VO2 deficit and the duration of the VO2 deficit was greatest in nonsurvivors, less in survivors with organ failure, and least in survivors without organ failure. Although many associated clinical conditions as well as innumerable physiologic mechanisms and biochemical mediators play important roles in tissue injury, tissue oxygen debt reflected by insufficient VO2 appears to be the primary event as well as a major determinant of organ failure and outcome.