Patients undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (for example heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT) but it is associated with an increased risk of bleeding. Mechanical prophylaxis (for example antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has no side effects. However, it is not always appropriate in patients with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis and whether this is one treatment alone or in combination with another. To date, no systematic review has been conducted examining the effectiveness of thromboprophylaxis in preventing VTE in people undergoing amputation.