ObjectiveTo examine the characteristics and outcomes among patients with high-risk pulmonary embolism (PE) and malignancy. Patients and MethodsThe Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2019. The main outcome was the difference in all-cause in-hospital mortality. ResultsAmong 28,547 weighted hospitalizations with high-risk PE, 4,825 (16.9%) had malignancy. Admissions with malignancy had a lower prevalence of other comorbid conditions except for anemia and coagulopathy. The use of systemic thrombolysis, catheter-directed interventions, and surgical embolectomy was less common among admissions with malignancy, whereas the use of inferior vena cava filter was more common among those with malignancy. All-cause in-hospital mortality was higher among admissions with malignancy even after adjustment (adjusted odds ratio, 1.91; 95% CI, 1.72 to 2.11; P<.001). Metastatic genitourinary, gastrointestinal (other than colorectal), and lung malignancies were associated with the highest incidence of in-hospital mortality. The incidence of intracranial hemorrhage (3.9% vs 3.1%; P=.056) and the composite of non–intracranial hemorrhage bleeding (21.9% vs 20.6%; P=.185) was not different between admissions with and without malignancy. However, admissions with malignancy had higher incidence of gastrointestinal bleeding. ConclusionIn this nationwide analysis of patients admitted with high-risk PE, malignancy was independently associated with an increased risk of in-hospital mortality. The risk was highest among patients with metastatic genitourinary, gastrointestinal, and lung malignancies. Advanced therapies were less frequently used among patients with malignancy.