Argatroban, a hepatically metabolized direct thrombin inhibitor, is approved for anticoagulation in patients with or at risk of heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). We investigated the effect of renal function on argatroban therapy during PCI. From previous argatroban studies in PCI, we evaluated relationships between estimated creatinine clearance (CrCl) and activated clotting times (ACTs), dosage, and outcomes in 219 patients with or at risk of HIT (HIT group, n = 67) or administered glycoprotein IIb/IIIa inhibition (non-HIT group, n = 152). Patients received an argatroban bolus (350 mcg/kg, HIT group; 250 or 300 mcg/kg, non-HIT group) then 25-30 mcg/kg/min (adjusted to achieve ACTs 300-450 s, HIT group) or 15 mcg/kg/min (target ACTs 275-325 s, non-HIT group), with additional 150-mcg/kg boluses if needed. Of 219 patients, 55 (25%) had CrCl <or= 60 ml/min (8 with CrCl <or= 30 ml/min). Regression analyses detected no association between CrCl (range 7-231 ml/min) and initial ACT (by bolus) or mean infusion dose. Multi-bolus usage was similar in patients with, versus without, CrCl <or= 60 ml/min. In the non-HIT group, CrCl was associated (P = 0.01) with the time to ACT <or= 160 s after argatroban cessation (approximately 17 min slower per 30-ml/min CrCl decrease). Eight patients (none with CrCl <or= 60 ml/min) had ischemic complications. Three patients (1 with CrCl 40 ml/min) experienced major bleeding. Argatroban dose adjustment for renal function appears unnecessary during PCI. Renal dysfunction may be associated with slower (by minutes) ACT effect decay after argatroban cessation. Argatroban is well tolerated in PCI patients with renal impairment.