OBJECTIVE: Despite proven blood transfusion benefits, aprotinin may be underused in coronary artery bypass grafting. Reluctance to use aprotinin may stem from safety concerns. The current objective was to evaluate clinical outcomes (mortality, myocardial infarction, renal failure, stroke, atrial fibrillation) in patients undergoing coronary artery bypass grafting who receive aprotinin by performing a quantitative overview of published, randomized, controlled trials. METHODS: MEDLINE, EMBASE, and PHARMLINE (1988-2001) and reference lists of relevant articles were searched for coronary artery bypass grafting studies. Criteria for data inclusion were as follows: (1) random allocation of study treatments, (2) placebo control, (3) enrollment only of patients undergoing coronary artery bypass grafting, (4) no combination with another experimental medication or device, and (5) prophylactic and continuous intraoperative use. RESULTS: Data from 35 coronary artery bypass grafting trials (n = 3879) confirm that aprotinin reduces transfusion requirements (relative risk 0.61, 95% confidence interval 0.58-0.66) relative to placebo, with a 39% risk reduction. Aprotinin therapy was not associated with increased or decreased mortality (relative risk 0.96, 95% confidence interval 0.65-1.40), myocardial infarction (relative risk 0.85, 95% confidence interval 0.63-1.14), or renal failure (relative risk 1.01, 95% confidence interval 0.55-1.83) risk, but it was associated with a reduced risk of stroke (relative risk 0.53, 95% confidence interval 0.31-0.90) and a trend toward reduced atrial fibrillation (relative risk 0.90, 95% confidence interval 0.78-1.03). CONCLUSIONS: Aprotinin reduces transfusion requirements. Concerns that aprotinin therapy is associated with increased mortality, myocardial infarction, or renal failure risk is not supported by data from published, randomized, placebo-controlled clinical trials. Evidence for a reduced risk of stroke and a tendency toward reduction of atrial fibrillation occurrence was observed in patients who received aprotinin.