May-Thurner syndrome (MTS) has been recognized as a clinical entity for almost six decades. The true incidence rate of MTS is unknown and perhaps ranges from 22 to 32% according to the autopsy studies in the early twentieth century. However, MTS related deep venous thrombosis (DVT) accounts for only 2%-3% of all lower limb DVTS. In MTS, the left common iliac vein is compressed against the fifth lumbar vertebrae by the right common iliac artery, as it crosses in front of the vein. Chronic pulsation of the artery is thought to cause elastin, collagen deposition, and intimal fibrosis leading to formation of venous spur and venous thrombosis. MTS can present as acute or chronic DVT leading to pulmonary embolism (PE), chronic leg pain, chronic ulcers, or skin pigmentation changes. In this case report we have described an interesting case of a 28-year-old Caucasian female who presented for evaluation of shortness of breath (SOB) associated with cough for one week. SOB was found to be secondary to massive bilateral pulmonary embolism resulting from extensive MTS related DVT of the left lower extremity. Patient underwent pharmacomechanical treatment with local thrombolysis, thrombectomy, and venoplasty along with stent placement that extended to inferior vena caval junction. Subsequently patient was discharged on coumadin. MTS should be considered in differentials when faced with a case of unilateral DVT particularly in younger age group.