The evolution of percutaneous procedures that use transseptal puncture to treat left-sided structural heart disease has led to the emergence of iatrogenic atrial septal defects as a potential complication. These defects can result in hemodynamic decompensation and worsening clinical outcomes. Some iatrogenic atrial septal defects require immediate closure, others do not. This case report presents 2 patients who underwent transcatheter edge-to-edge mitral valve repair with transseptal puncture and required iatrogenic atrial septal defect closure (1 immediate and 1 delayed). The goal of this report is to highlight iatrogenic atrial septal defect assessment and the possible need for closure after transseptal puncture.