Transcatheter edge-to-edge mitral valve repair with MitraClip System (Abbott Vascular, Menlo Park, CA) needs a trans-septal access for positioning the 22-Fr guiding catheter in the left atrium. To the best of our knowledge no data are currently available about the hemodynamic consequences of a congenital atrial septal defect (ASD) after MitraClip repair. We report a case of MitraClip repair in a patient with ostium secundum ASD and ischemic cardiomyopathy, who needed intraprocedural closure of the defect for serious hemodynamic complications, secondary to worsening of the right ventricular function, increased pulmonary pressure and inversion of the interatrial shunt in right-to-left direction. These events, which were exacerbated by high blood levels of PaCO2 for the anesthesiological protocol used, led to left-side low-output syndrome and cardiorespiratory arrest. © 2015 Wiley Periodicals, Inc.