Graft occlusion following peripheral vascular surgery is attributable to some combination of acute thrombosis, and progression of atherosclerosis: interactions between leukocytes and activated platelets may play a role in both of these processes. This investigation measured perioperative leukocyte-platelet conjugate formation, and leukocyte and platelet activation in 46 patients undergoing surgery for lower extremity peripheral vascular disease (PVD). All patients were followed for graft patency over the next 6 months; 27 patients had grafts that remained patent while 19 had graft occlusion. On postoperative day #1 (POD#1), the graft occlusion group demonstrated a significantly greater increase in circulating levels of both monocyteplatelet and neutrophil (PMN)-platelet conjugates compared to the patent graft patients (p=0.015 and 0.018, respectively). PMN activation, assessed by increases in surface CD11b expression, was also significantly increased on POD#1 in the graft occlusion group compared to the patent group (p=0.026). The percentage of circulating activated (CD62P+) platelets did not differ between groups, but patients with graft occlusion demonstrated a higher percentage of younger, reticulated plate-lets throughout the study period (p=0.008), indicating increased platelet turnover. We conclude that in the early postoperative period, leukocyte-platelet adhesion, PMN activation, and platelet turnover are significantly greater in PVD patients who go on to develop later graft occlusion. Cellular activation and heterotypic cell interactions in peripheral vascular surgery patients may be important in the etiologies of thrombosis and/or accelerated atherosclerosis leading to graft loss.