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A minority of patients who experience postoperative complications die (failure to rescue). Understanding the preoperative factors that lead to failure to rescue helps surgeons predict and avoid operative mortality.To provide a mechanism for identifying a high-risk group of patients with postoperative complications who are at a substantially increased risk for failure to rescue.Observational study evaluating failure to rescue in patients entered into the American College of Surgeons National Surgical Quality Improvement Program database. The large sample of surgical patients included in this study underwent a wide range of operations during a 5-year period in more than 200 acute care hospitals. We examined and identified patients at high risk for failure to rescue using propensity stratification. We also developed a risk-scoring system that allowed preoperative identification of patients at the highest risk for failure to rescue.Risk-scoring system that predicts failure to rescue.Of the 1 956 002 database patients, there were 207 236 patients who developed serious postoperative complications. Deaths occurred in 21 731 patients with serious complications (10.5% failure to rescue). Stratification of patients into quintiles, according to their propensity for developing serious complications, found that 90% of operative deaths occurred in the highest-risk quintile, usually within a week of developing the initial complication. A risk-scoring system for failure to rescue, based on regression-derived variable odds ratios, predicted patients in the highest-risk quintile with good predictive accuracy. Only 31.8% of failure-to-rescue patients had a single postoperative complication. Perioperative deaths increased exponentially as the number of complications per patient increased. Patients with complications who had surgical residents involved in their care had reduced rates of failure to rescue compared with patients without resident involvement.Twenty percent of high-risk patients account for 90% of failure to rescue (Pareto principle). More than two-thirds of patients with failure to rescue have multiple complications. On average, a few days elapse before death following a complication. A risk-scoring system based on preoperative variables predicts patients in the highest-risk category of failure to rescue with good accuracy. In high-risk patients who develop complications, our results suggest that early intervention, preferably in a high-level intensive care facility with a surgical training program, offers the best chance to reduce failure-to-rescue rates.