Rationale: There are few follow-up studies on long-term cardiopulmonary function after pulmonary endarterectomy (PEA), the operation of choice for chronic thromboembolic pulmonary hypertension (CTEPH). Objectives: To prospectively evaluate long-term outcome of CTEPH patients treated with PEA. Methods: Between 1994 and 2006, 157 patients (mean age 55 years) were treated with PEA at Pavia University Hospital. The patients were evaluated before PEA and at 3 months (n=132) and 1 year (n=110), 2 years (n=86), 3 years (n=69), and 4 years (n=49) afterward by NYHA class, right heart hemodynamic, spirometry, carbon monoxide transfer factor (T_Lco), arterial blood gas, and treadmill incremental exercise test. Results: Cumulative survival was 84%. Within 3 months, 18 died in-hospital and 2 had lung transplantation; during long-term follow-up, 6 died, 1 had lung transplantation and 3 had a second PEA (2.5 events per 100 person year). NYHA class III-IV was the most important predictor of late death, lung transplant or PEA redo (HR 3.94). Extraordinary improvement in NYHA class, hemodynamic, and PaO₂ were achieved in the first 3 months (p<0.001) and persisted during followup; exercise tolerance progressively increased over time (p<0.001). At 4 years, although 74% of the patients were in NYHA class I and none was in class IV, 24% had PVR >500 dyne.s/cm⁵ or PaO₂<60 mmHg; they were significantly older and were more frequently in NYHA class III-IV 3 months after surgery than the others. Conclusions: After PEA, long-term survival and cardiopulmonary function recovery is excellent in most patients.