Background: The present study evaluates the impact of procedural volume on intraoperative and short-term outcomes of endovascular aneurysm repair (EVAR) using the AFX2 unibody endograft in a large, multicenter cohort. Methods: A secondary analysis of the AFX2 LIVE study was conducted, including 535 EVAR procedures performed across 43 centers from November 2019 to August 2021. Centers were categorized into four quartiles based on case volume. Procedural efficiency (operative time, fluoroscopy time, contrast media use) and clinical outcomes (technical success, 30-day clinical success, major adverse events) were analyzed. A nonlinear regression model identified a volume threshold for improved technical outcomes. Results: Higher-volume centers demonstrated significantly shorter operative times (Q1= 80 min vs. Q4= 60 min, P=0.003), reduced contrast media usage (Q1=89.6 mL vs. Q4=61.9 mL, P=0.001), and lower fluoroscopy times (Q1=714 s vs. Q4=520 s, P=0.001). Logistic regression indicated that each additional 10 cases increased the likelihood of optimal procedural performance (OR=1.29, P=0.001). A threshold of 30 cases per center was identified, above which the probability of achieving optimal technical outcomes exceeded 50%. Despite these efficiency improvements, primary technical success (Q1-2=97.9% vs. Q3-4=98.0%, P=0.928) and 30-day MAE rates remained comparable across all quartiles. Conclusions: Institutional experience significantly influences procedural efficiency in EVAR with the AFX2 device, with a learning curve effect evident beyond 30 cases. However, technical success and safety remain high across all centers, reinforcing the device's feasibility even in lower-volume institutions. These findings support current European guidelines recommending a minimum annual EVAR caseload of 30 procedures per center. (Cite this article as: Andreoli F, Sirignano P, Gaggiano A, Acciarino G, Tusini N, Benedetto F, et al.; AFX2-LIVE Collaborative Study Group. Impact of center experience on unibody anatomically fixed systems utilization: insight from a multicentric, international, non-randomized, prospective registry-the AFX2-LIVE Study. J Cardiovasc Surg 2025 Sep 11. DOI: 10.23736/S0021-9509.25.13337-5)