Massive pulmonary embolism (PE) is not an uncommon condition, and it usually carries a high risk of mortality. It is one of the fatal conditions that commonly affect young patients. A definitive treatment for patients with massive PE is still lacking, and surgical intervention carries a substantial mortality risk. Thus, percutaneous intervention (clot fragmentation and/or aspiration) remains an option in some patients, specifically in those with a risk of bleeding, contraindicating the use of thrombolysis. There have been no randomized trials to validate percutaneous intervention in massive PE. A sufficient level of evidence is still lacking, and its use depends upon the expert committee's opinion and study of previous case reports. We present a 23-year-old man with first onset massive PE secondary to protein C deficiency, who was treated successfully with the combination of systemic thrombolysis and percutaneous interventions.