Trauma, immobilization, and subsequent surgery of the hip and lower limb are associated with a high risk of developing venous thrombo-embolism (VTE). Individuals undergoing hip fracture surgery (HFS) have the highest rates of VTE among orthopedic surgery and trauma patients. The risk of VTE depends on the type and location of the lower limb injury. Current international guidelines recommend routine pharmacological thromboprophylaxis based on treatment with heparins, fondaparinux, dose-adjusted vitamin K antagonists and acetylsalicylic acid for patients undergoing emergency HFS; however, not all guidelines recommend pharmacological prophylaxis for patients with lower limb injuries. Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for VTE prevention after elective hip or knee replacement surgery, but at present are not widely recommended for other orthopedic indications despite their advantages over conventional anticoagulants and promising real-world evidence. In patients undergoing HFS or lower limb surgery, decisions on whether to anticoagulate and the most appropriate anti-coagulation strategy can be guided by weighing the risk of thromboprophylaxis against the benefit in relation to each patient’s medical history and age. In addition, the nature and location of the fracture, operating times and times before fracture fixation should be considered. The current review discusses the need for anticoagulation in patients undergoing emergency HFS or lower limb surgery together with the current guidelines and available evidence on the use of NOACs in this setting. Appropriate thromboprophylactic strategies and practical advice on the peri-operative management of patients who present to the Emergency Department on a NOAC before emergency surgery are further outlined.