In his excellent “point” discussion, Dr Jiménez1 agrees with our position that studies have not convincingly demonstrated the superiority of thrombolysis on clinical outcomes in patients with acute pulmonary embolism (PE). He appropriately notes the limitations of the Management Strategies and Prognosis of Pulmonary Embolism Trial-3 (MAPPET-3), which, although interpreted by some physicians as supporting lytic therapy for submassive PE, did not show a mortality benefit of initial therapy with a lytic agent and, in fact, demonstrated the unsurprising finding that physicians (who could unblind the study assignment) were less likely to give additional lytic therapy to patients who had already received it (the main driver of the difference in the “escalation of therapy” end point).2 He highlights the poor positive predictive value for PE-related in-hospital death of a single echocardiographic criterion, the most common method used for classifying PEs as submassive. He confirms the low PE-related mortality among patients with submassive PE, as commonly defined, who are treated with heparin, and the approximately 2% risk of intracranial hemorrhage with lytic therapy, factors that, combined, make any mortality benefit from lysis unlikely. His excellent review of the data leads to his conclusion that lytic therapy should be limited to only the most severely compromised, highest-risk patients with submassive PE, who also lack contraindications to such treatment. Implicit in this conclusion that lytic therapy should be limited to such a subgroup is his lack of support for administering lytic therapy to the broader population of patients with submassive PE, who, as currently defined, may comprise more than one-half of all normotensive patients with acute PE.