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Published data suggest that permissive anemia strategies that allow nadir hemoglobin (nHb) values of 7 g/dL or lower are safe in a variety of clinical settings. The appropriateness of these strategies in patients at high risk for adverse postoperative cardiac events remains unclear. We sought to determine the combined effect of postoperative nHb and cardiac risk status on major complications after vascular surgical interventions.This was a single-institution retrospective analysis of consecutive patients who underwent elective open procedures for occlusive vascular disease and aneurysm repair, either open or endovascular. The Revised Cardiac Risk Index (RCRI) was used to assess baseline cardiac risk. Primary outcome was a composite end point of mortality or major ischemic events (myocardial infarction, stroke, acute kidney injury, or coronary revascularization) within 90 days from the index operation. Secondary outcomes included intensive care unit (ICU) length of stay (LOS) and 90-day respiratory complications (pneumonia, ventilator dependence for >48 hours postoperatively, or reintubation). Hierarchical multivariable regression was used to model each outcome with adjustment for age, type of operation, baseline comorbidities, and intraoperative covariates.We analyzed 2508 operations performed during 8 years in 2106 patients with a mean age of 67 years (range, 45–90 years). In the fully adjusted multivariable model, lower values of nHb increased the risk of the primary composite end point (odds ratio [OR], 1.24; P < .001, representing a 24% increase in the odds of the composite end point for each 1-g/dL increase in nHb). In the same model, RCRI class II (OR, 1.8; P < .001), class III (OR, 2.06; P < .0001), and class IV (OR, 2.35; P < .0001) were associated with progressively increasing odds of the composite end point compared with RCRI class I. An interaction term between transfusion and nHb was not significant statistically, indicating that the harmful effect of anemia was independent of blood transfusion. Lower values of nHb also increased the risk of respiratory complications (OR, 1.41; P = .002) and ICU LOS (average 2.6-day increase per 1-g/dL increase of nHb; P < .0001).Postoperative anemia increases the rate of early postoperative mortality and major ischemic events, particularly in patients at higher baseline cardiac risk. It also adversely affects respiratory complications and ICU LOS. Until a randomized trial definitively settles the issue, restrictive transfusion strategies should be practiced with caution in patients undergoing major vascular interventions.