Background: Intermediate-high-risk (IHR) pulmonary embolism (PE) is defined by right ventricular (RV) dysfunction and elevated cardiac troponin in the absence of hemodynamic instability. While full-dose thrombolysis may improve outcomes, it poses a high bleeding risk. This study assessed the safety and efficacy of a reduced-dose, slow-infusion thrombolytic regimen. Methods: This single-center retrospective study included 124 patients with acute IHR PE who met at least one of the following criteria: systolic blood pressure <=110 mm Hg, heart rate >100 bpm, SpO2 <90% on room air, respiratory rate >20/min, or lactate >2 mmol/L. Patients with contraindications to thrombolysis or symptom onset >14 days were excluded. Patients received 25 mg intravenous alteplase (t-PA) infused over 4-6 hours, along with standard anticoagulation according to the institutional protocol. Following the initial dose, a repeat infusion of 25 mg over 4-6 hours was administered if tachycardia, hypoxia, or signs of organ hypoperfusion persisted on re-evaluation. Results: Syncope was the presenting symptom in 27.4%, and 49.2% had deep vein thrombosis. Median t-PA dose was 50 mg and median infusion duration was 6 hours. Significant improvements were observed in RV and RA size/function, thrombus burden, and clinical parameters (all P < .001). Qanadli score and RV/LV ratio decreased by 55% and 29%, respectively. Major and minor bleeding occurred in 4.8% and 3.2%. In-hospital mortality was 4.8%; 12-month survival was 89.5%. Chronic thromboembolic pulmonary hypertension developed in 3.2%. Conclusion: Low-dose, slow-infusion t-PA therapy appears effective and well-tolerated, offering hemodynamic and clinical benefit with fewer bleeding complications in patients with IHR PE.