© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.Recombinant tissue plasminogen activator (rt-PA) is the most commonly used thrombolytic agent in patients with high risk and intermediate to high mortality risk acute pulmonary embolism (PE). Clinical trials have shown early efficacy and safety of low-dose rt-PA. This study investigated the effects of low-dose rt-PA treatment on acute PE in long-term prognosis, recurrence of pulmonary thromboembolism, or the development of late complications. In this study, 48 patients undergoing low-dose rt-PA for the relative contraindications of thrombolytic therapy and 48 patients undergoing standard-dose therapy were evaluated retrospectively. Long-term follow-up investigated the chronic PE, recurrence, and causes of morbidity and mortality. In both treatment groups, embolism-induced mortality and overall mortality rates were similar in the first 30 days (p=1.000, p=0.714, respectively). Overall mortality rates in long-term follow-up were 41.7% in the low-dose treatment group and 16.7% in the standard-dose treatment group (p=0.013). The mortality rate at the first year was higher in the low-dose-treated group (p=0.011) and most of the deaths were due to accompanying comorbidities. There was no difference in PE recurrence and duration of recurrence between the groups (p=0.598, p=0.073, respectively). Intracranial hemorrhage due to therapy developed in one patient in both groups. Low-dose thrombolytic therapy in acute PE reduces PE-related mortality in the early period. Long-term follow-up showed that thrombolytic therapy did not affect mortality rates independently of the dose and PE recurrence.