A 52-year-old non-smoking Caucasian male, who was admitted to our emergency room after he was found unconscious in the bathroom, went into cardiac arrest requiring prolonged cardiopulmonary resuscitation (CPR) and hypothermia therapy. Cardiac catheterization showed non-obstructive coronary arteries and further bedside echocardiogram suggested probable pulmonary embolism (PE) as an underlying cause of cardiac arrest. Although thrombolytic therapy is an effective therapy for PE, it is not routinely given during prolonged CPR for its life- threatening bleeding complications. Many reported cases have suggested a beneficial effect of empiric thrombolytic in cardiac arrest, but unrelated to duration of resuscitation and adjuvant treatments that imposes bleeding risk. We suspect that tissue plasminogen activator (tPA) should be promptly given to prolonged cardiac arrest patients, even when bleeding risk is high with the concurrent hypothermia treatment, keeping the benefits over risk strategy. Our patient received thrombolytic, tPA and showed remarkable clinical, physiological and radiographical improvement.