Background We retrospectively evaluated vascular complications and wound infections after surgical or percutaneous transfemoral removal of temporary extracorporeal life support systems (ECLSs). Methods A total of 83 patients were weaned from ECLS between August 2015 and September 2020. We analyzed for a composite endpoint of vascular complications and wound infections requiring negative-pressure wound therapy. Patients were divided into two groups: percutaneous group using the MANTA vascular occlusion system (VCD; Teleflex, Morrisville, North Carolina, United States) (n = 23) and surgical group (n = 60). Results The median age in the entire cohort was 67 years. Vascular complications were seen in 20% (n = 12) in the surgical group and in 13% (n = 3) in the percutaneous group (p = 0.72). A total of 32% (n = 19) in the surgical group and 9% (n = 2) in the percutaneous group (p = 0.031) had wound infections. A composite endpoint of vascular complications and wound infections showed significantly more complications in the surgical group (52%, n = 31) as compared with the percutaneous group (22%, n = 5) (p = 0.020). The median duration in the intensive care unit was 13 days for the surgical group and 12 days for the percutaneous group without any significant difference in both groups (p = 0.93). Conclusions Using the MANTA VCD for percutaneous removal of ECLS cannulas after weaning from ECLS is safe and reproducible. A composite endpoint of vascular complications and wound infections was significantly lower in the percutaneous removal group as compared with the surgical group. C.P., MD: Substantial contributions to the conception and design of the work, acquisition, analysis and interpretation of data for the work. Drafting the work and revising it critically for important intellectual content, and final approval of the version to be published. S.K., MD: Substantial contributions to the acquisition, analysis and interpretation of data for the work, revising the work critically for important intellectual content, and final approval of the version to be published. H.S., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content, and final approval of the version to be published. M.K., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content, and final approval of the version to be published. P.P., MD: Substantial contributions to the acquisition, analysis and interpretation of data for the work. Revising it critically for important intellectual content and final approval of the version to be published. S.K., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content. Final approval of the version to be published. T.B., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content. Final approval of the version to be published. F.B., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content. Final approval of the version to be published. M.S., MD: Substantial contributions to the conception of the work and revising it critically for important intellectual content. Final approval of the version to be published. M.C., MD: Substantial contributions to the conception and design of the work, acquisition, analysis, and interpretation of data for the work, drafting the work and revising it critically for important intellectual content, and final approval of the version to be published. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Received: 11 December 2020 Accepted: 05 March 2021 Publication Date: 10 August 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany