Risk stratification of pulmonary embolism (PE) is vital for clinical management. While low-risk and high-risk PE management are clearly defined in many societal guidelines, the management of moderate-risk, also called submassive, PE remains unsettled. There is a subgroup of patients with submassive PE that progress to the severe category despite receiving systemic anticoagulation. The role of thrombolysis in the management of submassive PE remains to be established. We share our experience with ultra-low-dose (25-mg) systemic tissue plasminogen activator in a series of 4 patients with high-risk submassive PE.