Background: Venous thromboembolism (VTE) is a considerable public health threat. Improving the management of VTE may achieve better long-term outcomes. In this single-center pilot study, we sought to investigate the effects of statins in addition to anticoagulation in patients with acute VTE.Methods: We enrolled patients over the age of 18 presenting with an acute proximal lower extremity deep vein thrombosis with or without pulmonary embolism. Patients were randomized to anticoagulation alone (with either warfarin or rivaroxaban) or anticoagulation plus atorvastatin 40 mg daily and followed for 9 months. The primary objective was to determine if adjunct atorvastatin reduced thrombin generation, estimated by endogenous thrombin potential and/or peak thrombin concentration. Secondary endpoints included recurrent VTE, arterial thrombosis, bleeding events, and more.Results: A total of 21 patients (11 randomized to anticoagulation only and 10 to anticoagulation plus atorvastatin) were enrolled over 3.5 years. The addition of atorvastatin significantly reduced the mean low-density lipoproteins at 3 months, but did not reduce either endogenous thrombin potential, peak thrombin, D-dimer, or high sensitivity-C reactive protein. Given the low recruitment rate, continuation of the study was deemed futile and the study was terminated early. Barriers to enrollment and completion of study included the many ineligible patients due to the exclusion criteria (e.g. pre-existing statin use, active malignancy, etc) and high rate of lost follow-up.Conclusions: The pilot study did not enroll sufficient number of patients, but was able to inform obstacles for future similar studies investigating the effects of statins in the management of patients with VTE.Trial registration: The study was registered with ClinicalTrials.gov (NCT02331095), January 6, 2015. https://clinicaltrials.gov/ct2/show/NCT02331095