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Background: A paravalvular leak (PVL) is a complication following valve replacement, which may lead to heart failure and hemolysis. The aim of this study is to investigate whether the clinical outcome after transcatheter PVL closure differs according to the prominent indication of the procedure (symptoms of heart failure or hemolysis). Methods: The data of consecutive patients who had transcatheter treatment for PVL between July 2011 and September 2022 in five Greek centers were analyzed. The primary endpoint was the technical, and clinical success rates with regards to the prominent indication of paravalvular leak closure. The secondary endpoints included the evaluation and comparison of the clinical and technical success in relation to the type of valve that was treated (aortic or mitral) as well as the survival analysis in relation to the closure indication and type of valve that was treated. Results: In total, 60 patients were retrospectively studied (39% men, mean age 69.5 ± 11 years). Regarding the primary outcomes, the technical success in patients mainly suffering from hemolysis was 86.1%, while in those presenting heart failure it was 95.8%, p = 0.387. Furthermore, the clinical success was 72.2% and 87.5% among hemolysis and heart failure patients, respectively, p = 0.210. During the follow-up period, the two-year survival rates were significantly better for patients treated for the aortic valve (78.94%) compared to those in the mitral position (48.78%), p = 0.014. In total, 25 patients died (41.7%) during 24 months of follow-up. Conclusions: Transcatheter paravalvular leak closure can be performed with high technical and clinical success rates without any difference according to the prominent indication of closure.