Abstract Background There is an incentive to centralize specialized health care, which particularly applies to high-risk surgical and trans-catheter cardiovascular procedures. In health care policy, annual hospital case volume is the main criterion to define expertise and determine centralization. Purpose We propose a novel methodology to evaluate the volume-outcome relation for high-risk and infrequent cardiovascular procedures, by use of a meta-analytical approach, and aim to determine a specific annual case volume threshold, using surgery for acute type A aortic dissection (ATAAD) as an example. Methods This study was designed as a systematic review and meta-analysis (PROSPERO; registration number CRD42022345024). We included studies reporting on (i) consecutive ATAAD patients, (ii) years of inclusion and (iii) early mortality. The primary outcome was early mortality in relation to annual hospital case volume. Secondary outcome was long-term survival. Data were presented and compared in volume quartiles (Q's, Q1 1-12, Q2 12-17, Q3 17-28, and Q4 28-241 cases/year). Restricted cubic spline analysis was used to demonstrate the volume-outcome relation. Derived from optimization statistics, we introduce the concept of the 'elbow-method' to determine the optimal annual case volume (see Figure 1). For long-term survival, individual patient data derived from Kaplan-Meier curves were integrated. For clinical interpretation, numbers needed to treat (NNT) were calculated. Results 125 studies from 125 unique centers were included (25 countries, 5 continents, see Figure 1), comprising 33 027 patients. A significant between-quartile difference for early mortality was observed (10.5% [Q4] vs. 16.8% [Q1], p<0.001, I2=72%), which persisted after correction for age, sex, and dissection type (p<0.001). Furthermore, a significant non-linear volume-outcome association was observed as well (p<0.001, Figure 1). The optimal annual case volume after which results did not improve any further, was determined at 41 cases/year (95% CI 39-45, relative risk reduction 37.1%, NNT 16.1, compared to 10 cases/year, Figure 1). Even more pronounced between-quartile survival differences were observed for long-term survival (43 studies, n=11 704, 10-year survival Q4 69% vs Q1 56%, p<0.001, HR=0.87, 95%CI=0.84-0.90, p<0.001, NNT 6.7, Figure 2). This notable long-term survival difference persisted after correction for age, sex, and dissection type (Figure 2). Conclusions High volume centers exhibit superior results in surgery for ATAAD, compared to lower volume centers. Using a novel approach, the optimal annual hospital ATAAD case volume threshold was statistically determined at 41 cases/year, with a high degree of certainty. Despite its acute character, rerouting of patients and centralization of ATAAD care in high-volume centers may lead to improved outcomes. This novel method has the potential to be applied to various other cardiovascular procedures requiring centralization.Figure 1Early mortalityFigure 2Long-term survival