Background: Pulmonary tumor thrombosis can be a catastrophic manifestation of many solid tumors more so in gestational trophoblastic disease. Trophoblastic pulmonary embolism and subsequent pulmonary hypertension can lead to severe cor pulmonale. The role and utility of pulmonary vasodilators in this setting are not very well established since the etiology is considered tumor thrombosis. Most patients present with bleeding diathesis which precludes the use of anticoagulants. We suggest that the use of pulmonary vasodilators should be individualized as it can improve survival in select high-risk cases. Case description: A 35-year-old female with high-risk gestational trophoblastic neoplasm with lung metastasis presented with fever, dyspnea cough, and hemoptysis. She had a history of molar pregnancy which was evacuated under general anesthesia 6 months back. Transthoracic echocardiography showed acute cor pulmonale with severe pulmonary hypertension [pulmonary artery systolic pressure (PASP) 69 mm Hg] and the computed tomography pulmonary angiogram (CTPA) revealed a large tumor thrombus in the right pulmonary artery. She was started on sildenafil 10 mg bd for which she responded well with reduced PASP (45 mm Hg). She was discharged from the intensive care unit (ICU) on day 6. Conclusion and clinical significance: Trophoblastic pulmonary thrombosis causing pulmonary hypertension and acute right heart failure can be a life-threatening condition. In spite of the multifactorial etiology of thrombosis and microangiopathy, the use of pulmonary vasodilators can be lifesaving and their use should be individualized as this may benefit high-risk patients.