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To develop and validate a preoperative risk index for predicting postoperative respiratory failure (PRF).Respiratory failure is an important postoperative complication.Based on a prospective cohort study, cases from 44 Veterans Affairs Medical Centers (n = 81,719) were used to develop the models. Cases from 132 Veterans Affairs Medical Centers (n = 99,390) were used as a validation sample. PRF was defined as mechanical ventilation for more than 48 hours after surgery or reintubation and mechanical ventilation after postoperative extubation. Ventilator-dependent, comatose, do not resuscitate, and female patients were excluded.PRF developed in 2,746 patients (3.4%). The respiratory failure risk index was developed from a simplified logistic regression model and included abdominal aortic aneurysm repair, thoracic surgery, neurosurgery, upper abdominal surgery, peripheral vascular surgery, neck surgery, emergency surgery, albumin level less than 30 g/L, blood urea nitrogen level more than 30 mg/dL, dependent functional status, chronic obstructive pulmonary disease, and age.The respiratory failure risk index is a validated model for identifying patients at risk for developing PRF and may be useful for guiding perioperative respiratory care.