We describe an unusual case of non-traumatic compartment syndrome in three compartments of the left lower limb in a 57-year-old male inpatient. He had recently been started on anticoagulation therapy for multiple pulmonary emboli and deep vein thrombosis of the left posterior tibial and peroneal veins. Three of the four osteofascial compartments had pressures above 70 mm Hg, hence four compartment fasciotomies were performed. Postoperatively, intravenous heparin therapy was started resulting in a significant blood loss, but he had no neurovascular deficit. At reoperation, for primary wound closure, his tissues looked healthy. Non-traumatic causes of acute compartment syndrome, including deep venous thrombosis and anticoagulation, are considered.