Venous thromboembolism (VTE), defined as deep vein thrombosis and/or pulmonary embolism is the second leading cause of mortality in cancer patients, second only to cancer itself. A number of reports suggest that circulating extracellular vesicles (EVs) may be increased in cancer patients with VTE. The aim of this study was to examine circulating EVs in high-risk ambulatory cancer patients, determine if levels are associated with hematological outcomes (VTE, major bleeding event), and to assess the impact of prophylactic antithrombotic therapy (Apixaban). We hypothesized that elevated levels of circulating large EVs will be predictive of cancer associated VTE and/or bleeding events and that treatment with Apixaban will reduce EV levels and incidence of cancer VTE. Plasma samples from patients at baseline, and 90-days follow-up from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer patients (AVERT) trial were investigated. Total EVs were quantified by their pro-coagulant activity using the Zymuphen MP-Activity kit. Platelet, endothelial and tissue-factor EV levels were quantified by flow cytometry. We observed that circulating EVs exhibited significant associations with sex, age, and cancer type, however we did not observe any relationships with clinical outcomes. Thus, it appears that circulating EVs may not have a role in risk stratification for VTE in in high-risk ambulatory cancer patients.