Mortality with adjunctive therapy in patients with unstable pulmonary embolism, defined as those in shock or on ventilator support, is sparsely studied and requires further investigation. This was a retrospective cohort study based on administrative data from the Nationwide Inpatient Sample, 2016. In-hospital all-cause mortality in unstable patients with acute pulmonary embolism was assessed according to treatment. Patients were identified by International Classification of Diseases-10-Clinical Modification Codes. Most unstable patients, 85%, received only anticoagulants. Their mortality was 3,080 of 6,635 (46%) without an inferior vena cava (IVC) filter, and mortality was much less with an IVC filter, 285 of 1,185 (24%) (p <0.0001). Mortality with catheter-directed thrombolysis alone, 70 of 235 (30%), did not differ significantly from mortality with anticoagulants plus an IVC filter, p = 0.07, although a trend favored the latter. Intravenous thrombolytic therapy without an IVC filter showed a mortality of 295 of 695 (42%) which tended to be lower than mortality with anticoagulants alone (p = 0.06). The addition of an IVC filter to intravenous thrombolytic therapy resulted in a mortality of 20 of 165 (12%), which was the lowest mortality with any combination of adjunctive treatments. Intravenous thrombolytic therapy, however, was associated with more adverse effects of therapy than catheter-directed thrombolysis or anticoagulants.