Objective Pericardial patches for intraventricular repair are limited by progressive calcification, thickening, and retraction. The aim of this study was to evaluate the safety of CorMatrix extracellular matrix (ECM) for intraventricular repair of mechanical complications of myocardial infarction (MI). Methods CorMatrix ECM is a novel material synthesized from decellularized porcine small intestinal submucosa. Between July 2011 and October 2012, a total of 11 consecutive patients with post-MI complications including ventricular aneurysm (n = 7), ventricular septal defect (VSD; n = 3), and both aneurysm and VSD (n = 1) underwent patch repair using CorMatrix ECM. Clinical follow-up and interval transthoracic echocardiography data were collected. Results Eleven patients underwent Dor or linear left ventricular aneurysm repair and/or patch VSD repair. There were two reoperations and one surgical mortality but no cases of CorMatrix ECM repair failures. The mean ± SD clinical follow-up was 207 ± 211 days, and the longest follow-up was 642 days, during which there was no readmission for any cardiac cause or death. The mean ± SD transthoracic echocardiography follow-up was 176 ± 220 days, which demonstrated integrity of CorMatrix ECM repair in all cases. Conclusions In our series, CorMatrix ECM was a safe alternative for ventricular patch repair of mechanical complications after MI in the short-term. This series supports the continued study of the efficacy and the regenerative potential of this novel material for cardiac repair.