This prospective cohort study will involve patients undergoing major esophageal resection for esophageal cancer at 8 tertiary care centres across Canada, 3 centres in the USA, and 1 site in China. McMaster University at St. Joseph's Healthcare Hamilton will serve as the Coordinating Centre as well as a study site. Recruitment will commence at each site until 150 patients are enrolled via consecutive convenience sampling. After undergoing esophagectomy, all patients will receive both a peri-operative dose followed by post-operative LMWH VTE prophylaxis for the remainder of their hospital stay. As per current VTE prophylaxis guidelines, prophylaxis will be discontinued upon hospital discharge. VTE outcomes will be assessed using Computed Tomography with pulmonary angiography protocol at 30 and 90 days and bilateral venous Doppler ultrasounds at 30, 60 and 90 days after surgery. The role of D-Dimer will be investigated at the completion of neoadjuvant chemotherapy or radiotherapy (if applicable), at the completion of clinical staging, at post-operative day 1 and 5, and at each imaging follow-up visit. A future second phase study will be a randomized controlled trial that will evaluate the role of extended duration thromboprophylaxis post-discharge in reducing the incidence of VTE in this patient population. The proposed prospective cohort study to evaluate the incidence of VTE needs to be conducted first, in order to optimize patient selection and determine the sample size for the subsequent randomized controlled trial.