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Background & aims: While in recent years centralization of healthcare has become an important topic of discussion, finding a volume-outcome (V-O) relation and defining an optimal annual case volume has proven rather difficult for relatively rare and high-risk procedures. In this meta-analysis, we employed a recently developed statistical approach to determine this V-O relation for patients undergoing pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: We systematically searched three electronic databases for studies containing consecutive patients undergoing PEA until May 1st, 2024. Our primary outcome was early mortality, defined as 30-day mortality/in-hospital mortality. We applied restricted cubic spline interpolation to assess a possible non-linear volume-outcome relation. The optimal annual case volume was calculated using the Elbow Method. Data was presented in tertiles based on the distribution of the studies and their annual case volume (T1: 0-6 cases/year, T2: 6-15 cases/year, T3: 15-145 cases/year). To evaluate long-term survival, we reconstructed individual patient data derived from Kaplan-Meier (KM) curves, using KM-curves and numbers at risk reported by the included studies. Results: We identified 52 studies of 52 unique centers, including 11 325 PEA patients. The mean age was 52.3 years, mean preoperative mean pulmonary artery pressure 48.1 mmHg, mean cardiac index 2.3 L/min/m2 and mean pulmonary vascular resistance 11 Wood Units (WU). We successfully identified a non-linear V-O relation (p = 0.0437). Early mortality was significantly lower in the higher volume tertiles (T1: 11.6%, T2: 7.2%, T3: 5.2%, p<0.001). The optimal annual case volume was determined at 33 cases/year. Long-term survival was also positively affected by increasing caseload. 1- and 10-year survival were 89.7% and 75.9% for the overall cohort respectively, with a hazard ratio of 0.98 (95%CI 0.97-0.99) per case or 0.75 (95%CI 0.63-0.89) per tertile. Conclusion: An increase in annual case volume is associated with reduced early mortality as well as improved long-term survival. Furthermore, we were able to determine the optimal annual case volume of PEA. These results could provide a much-needed statistical basis to assess the need for centralization of PEA and contribute to the definition of a high-volume expert center.