The effectiveness and safety of aprotinin in cardiac surgery has been questioned. The study aim was to compare both the blood-sparing effect and side effects of aprotinin and tranexamic acid in patients undergoing pulmonary endarterectomy.Data were analyzed retrospectively for 200 consecutive patients who underwent pulmonary endarterectomy between October 2006 and September 2009. Pulmonary endarterectomy was performed with deep hypothermia (20°C) in all patients. Antifibrinolytic therapy changed from aprotinin to tranexamic acid in June 2008 after the withdrawal of aprotinin in the United Kingdom.Mean age was 55.9 years, and 58% of subjects were male. One hundred patients were studied in each group. Postoperatively, a higher incidence of seizures in the first 48 hours was seen with tranexamic acid compared with aprotinin (11% versus 4%, p = 0.06). This difference became statistically significant when excluding patients with structural brain lesions from both groups (7 versus 0, p = 0.02). Tranexamic acid patients had significantly higher median blood loss (700 mL versus 525 mL, p = 0.01). There was no significant difference between the groups in reexploration for bleeding, renal failure requiring hemofiltration, intensive care unit stay, median total stay in hospital, or in-hospital mortality.In our experience of patients undergoing pulmonary endarterectomy, the tranexamic acid group had a higher median blood loss and more seizures. The trend to increased seizure frequency in the tranexamic acid group may be a direct consequence of this treatment, consistent with other recently published reports.