An internal database and research methods were used to evaluate the impact of clopidogrel on cardiac surgical bleeding. This quality improvement initiative, led by the clinical nurse specialist, showed that preoperative exposure to clopidogrel was associated with significant increases in chest tube output, blood product use, and reoperation for bleeding rates that were 10-fold higher than for control patients (0.85% versus 8.3%, P = 0.027). Acute care costs averaged $2,680 more for patients who received clopidogrel (P = 0.1936). After implementation of an interdepartmental clinical practice guideline, preoperative exposure to clopidogrel dropped from 39% to 6.3% (P = 0.0000). This drop was accompanied by reductions in chest tube output, blood product use, and bleeding complications, with improved achievement of clinical benchmarks. The availability of internal evidence to support achievement of best practices was an essential factor in the implementation of this interdepartmental change. Comprehensive database systems and advanced practice nurses are highlighted as essential components of evidence-based programs.