Background: Peripheral artery disease is endemic in our globally aging population, with >200 million affected worldwide. Graft/stent thrombosis after revascularization is common and frequently results in amputation, major adverse cardiovascular events, and cardiovascular mortality. Optimizing medications to decrease thrombosis is of paramount importance; however, limited guidance exists on how to use and monitor antithrombotic therapy in this heterogeneous population. Thromboelastography with platelet mapping (TEG‐PM) provides comprehensive coagulation metrics and may be integral to the next stage of patient‐centered thrombophrophylaxis. This prospective study aimed to determine if TEG‐PM could predict subacute graft/stent thrombosis following lower extremity revascularization, and if objective cut point values could be established to identify those high‐risk patients. Methods and Results: We conducted a single‐center prospective observational study of patients undergoing lower extremity revascularization. Patients were followed up for the composite end point postoperative graft/stent thrombosis at 1 year. TEG‐PM analysis of the time point before thrombosis in the event group was compared with the last postoperative visit in the nonevent group. Cox proportional hazards analysis examined the association of TEG‐PM metrics to thrombosis. Cut point analysis explored the predictive capacity of TEG‐PM metrics for those at high risk. A total of 162 patients were analyzed, of whom 30 (18.5%) experienced graft/stent thrombosis. Patients with thrombosis had significantly greater platelet aggregation (79.7±15.7 versus 58.5±26.4) and lower platelet inhibition (20.7±15.6% versus 41.1±26.6%) (all P <0.01). Cox proportional hazards analysis revealed that for every 1% increase in platelet aggregation, the hazard of experiencing an event during the study period increased by 5% (hazard ratio, 1.05 [95% CI, 1.02–1.07]; P 70.8% platelet aggregation and/or <29.2% platelet inhibition identifies those at high risk of thrombosis with 87% sensitivity and 70% to 71% specificity. Conclusions: Among patients undergoing lower extremity revascularization, increased platelet reactivity was predictive of subacute postoperative graft/stent thrombosis. On the basis of the cut points of >70.8% platelet aggregation and <29.2% platelet inhibition, consideration of an alternative or augmented antithrombotic regimen for high‐risk patients may decrease the risk of postoperative thrombotic events.