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Excessive blood loss (EBL) is a common complication of cardiac surgery that is associated with adverse events. The objective of this before/after study was to determine whether the implementation of a protocol for management of cardiac surgical patients with EBL was associated with improved clinical outcomes.In November 2002, a protocol for prompt identification and aggressive management of cardiac surgical patients with EBL was implemented at our institution. The independent relationship between protocol implementation and adverse outcomes was measured by comparing the outcomes of patients who received ≥ 4 RBC (red blood cell) units within 1 day of surgery and were operated on before protocol implementation (2000–02) with those operated on after protocol implementation (2003–05), using multivariable logistic regression analysis to control for the effects of confounders. The primary outcome was a composite of adverse events that included death, renal failure, stroke, and sepsis. Bootstrapping was used to confirm the validity of the results.Of the 11 314 patients who underwent surgery during the study period, 1875 (16·6%) received ≥ 4 RBC units within 1 day of surgery, with 958 and 917 in the pre- and postprotocol periods, respectively. The composite adverse outcome occurred in 164 (17·1%) patients in the preprotocol period and 115 (12·5%) patients in the postprotocol period (P = 0·005). Protocol implementation was independently associated with reduced odds of the composite adverse outcome (odds ratio 0·67; 95% confidence interval 0·50, 0·91; P = 0·01). This estimate was stable in bootstrap sampling.Implementation of a protocol to manage EBL in cardiac surgery was independently associated with improved outcomes.