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Renal dysfunction is a common serious complication after cardiac surgery. Reports of proteinuria and hyperkalemia after cardiac surgery with ε-aminocaproic acid (EACA) have therefore raised concerns for renal safety. Since EACA renders these markers unreliable, we used perioperative change in creatinine clearance (DCrCl) to test the hypothesis that EACA is associated with greater reductions in creatinine clearance after heart surgery, particularly for patients with renal disease. We evaluated data from all elective primary coronary bypass patients during EACA introduction at our institution (July 1, 1991–December 31, 1992; 10 g iv bolus pre-cardiopulmonary bypass, then 1 g/h for 5 h). DCrCl was calculated using preoperative (CrPre) and postoperative peak serum creatinine values, using the Cockroft-Gault equation. Patients with CrPre ≥ 133 μmol/L were also separately analyzed. Evaluated patients (n = 1502, ±EACA; 581/905, 16 exclusions) included 233 with CrPre ≥ 133 μmol/L (±EACA; 98/135). Multivariate analyses confirmed several known risk factors, but no association between DCrCl and EACA in all patients (P = 0.66), and the subgroup with CrPre ≥ 133 μmol/L (P = 0.42).In a large population of primary Coronary Artery Bypass Graft including a subset with preoperative renal dysfunction, there were no postoperative reductions in creatinine clearance attributable to δ-aminocaproic (EACA) administration. This retrospective study suggests that moderate δ-aminocaproic acid dosing during cardiac surgery is safe for the kidney; however, this inference is based on a single marker of renal dysfunction and requires prospective confirmation using a variety of tests of renal function.