Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63-yr-old white female initially underwent successful placement of a Palmaz-Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase-coated hydrogel balloon (Hydro Plus). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no-reflow. Local urokinase delivery directly to the site of thrombus with catheter-based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re-establishing coronary flow in the setting of acute stent thrombosis.