BACKGROUND: Post-infarction ventricular septal rupture (PIVSR) is a rare mechanical complication, characterized by a dismal prognosis. Despite the widespread timely reperfusion and recent advances in management, short-term mortality of PIVSR remains high. The complexity of the hemodynamic profile, confusing evidence for the optimal timing for intervention, and lack of head-to-head trials, all make the management of such a condition very challenging. METHODS: The database of a tertiary cardiac center was retrospectively analyzed for PIVSR cases through the period from April 2015 to April 2023. Clinical, echocardiographic, and interventional data were explored. The primary outcome was 30-day mortality that was contrasted for surgical versus percutaneous repair. RESULTS: A total of 32 patients with PIVSR were identified. The median age was 65 years, 50% were males, 56% had diabetes, and 50% had cardiogenic shock (CS) on presentation, with a median time of 3 days from acute myocardial infarction (AMI) to PIVSR diagnosis. The median left ventricular ejection fraction (LVEF) was 38%. Culprit vessel patency was acutely restored in 26 patients (81%), while intra-aortic balloon pump (IABP) was inserted in 25 (78%). Upfront insertion of IABP (in the absence of CS) showed a trend towards improved survival (43% vs. 9%). PIVSR was surgically repaired in 15 patients (47%), while 9 (28%) underwent percutaneous device closure, with no significant difference in outcomes and with a median time to intervention of 21 days for both groups. The overall 30-day mortality rate was 44%. Acute kidney injury (AKI) was a significant predictor for 30-day mortality (odds ratio 7.5, 95%CI: 1.3 - 43.7, p = 0.028). CONCLUSION: PIVSR still carries a grave prognosis. Early surgical or percutaneous intervention seems associated with higher mortality, while upfront insertion of IABP for a safe deferral of repair beyond the acute phase may lead to better outcomes. Larger randomized studies are required to dictate the best management.