Low-molecular-weight heparin (LMWH) has been considered superior to unfractionated heparin in several facets such as more effective anticoagulant, more predictable bioavailability, and less bleeding complications. We report two cases of LMWH, enoxaparin-induced spontaneous intramuscular hematoma with compartment syndrome of the lower extremity in patients with cardiac problems. The patients were treated with enoxaparin (LMWH) as bridging anticoagulation before use of warfarin due to cardiac problems. At the average 3 days of enoxaparin treatment, large and painful swelling was noticed in the lower extremities without intramuscular injection or trauma. The patients were diagnosed as having compartment syndrome with large intramuscular hematoma by CT. The patients underwent immediate fasciotomy and hematoma evacuation, and recovered without any complications.