Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of venous thromboembolism (VTE).We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease.Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of deep vein thrombosis (DVT). Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed to evaluate the crude and adjusted 3-year risks of arterial thrombotic disease, recurrent VTE, and death.The sample comprised 510 patients. Isolated PE patients (n=63) had a distinct clinical profile from patients with other VTE phenotypes (n=447). Chronic obstructive pulmonary disease (COPD), peripheral artery disease, atrial fibrillation and coronary artery disease were significantly more prevalent among patients with isolated PE. Isolated PE patients had significantly higher risk (incidence rate ratio vs DVT-associated PE: 3.7 [95% confidence interval: 1.3-10.8], p=0.009; vs isolated DVT: 4.8 [1.7-14.3], p=0.001) of arterial thrombotic events (i.e. myocardial infarction, stroke/transient ischemic attack). After adjustment for clinical profile and medication intake, the risk of arterial thrombotic events for patients with isolated PE remained quadruple that of other VTE phenotypes (hazard ratio, HR: 4.1 [1.4-11.7], p=0.009).Patients with isolated PE are at higher risk for arterial thrombosis, and may require screening for arterial disease and development of novel therapeutic strategies.