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Aims: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken., Methods and Resuts: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality., Conclusion: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery., Competing Interests: Conflict of interest: B.R.C. has received speaking fees from Abbott Vascular. P.M. has provided expert testimony and worked as a speaker for Edwards Lifesciences. J.B. has worked as a proctor for Abbott Vascular. M.S.T. has worked as a consultant and received educational grants from Occlutech. He has worked as a consultant and proctor for Abbott Vascular. D.B.N. has worked as a proctor for Abbott Vascular. D.H.-S. has received travel support and worked as a proctor for Abbott Vascular and Boston Scientific; he has received consulting fees and participated in a data and safety monitoring board for Abbott Vascular. M.A.M. has received non-restrictive educational grants from Abbott Vascular and Terumo, and worked as a consultant for Daiichi Sankyo and Terumo. P.A.C. has worked as a proctor for Abbott Vascular, Gore Medical and Occlutech., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)