Early infragenicular vein graft thrombosis is associated with poor secondary patency, particularly when no correctable defect is identified. We have attempted to improve patency of thrombosed vein grafts by direct infusion of vasodilator and anticoagulant drugs after surgical thrombectomy. Among 212 infragenicular vein grafts, 16 (7.5%) required thrombectomy within 30 days of surgery (14 in situ saphenous vein, 1 composite vein, and 1 cephalic vein graft). Causes for failure were corrected in four (graft twist, intimal tear, suture failure, and external compression), resulting in prolonged patency. No cause for failure was apparent in the 12 remaining grafts after balloon catheter thrombectomy and arteriography. Two of these grafts occluded within 10 days despite multiple attempts at vein patch angioplasty, distal graft extension, and repeat thrombectomy with systemic anticoagulation. In the remaining 10 grafts, a small polyethylene catheter was placed in a proximal vein branch for direct intragraft drug infusion. Heparin (10 units/min) and nitroglycerin (50 micrograms/min) were the agents infused most frequently, for a mean duration of 52 hours after thrombectomy. Of these 10 infused grafts, 8 remained patent during a mean 17-month follow-up (range, 6 to 38 months). This was accomplished despite previous and repeated failures of thrombectomy and systemic anticoagulation in seven of these eight grafts. Two infused grafts rethrombosed within 30 days of infusion, resulting in amputation. No catheter-related complications occurred. Increased thrombogenicity, intimal injury, and spasm after balloon catheter thrombectomy may contribute to vein graft rethrombosis in the absence of technical defects. Direct intragraft infusion of nitroglycerin and heparin contributed to prolonged salvage of 80% of thrombosed vein grafts in this preliminary experience.