Percutaneous vascular closure devices have become increasingly common in their use in both cardiac and peripheral vascular intervention. Our cases present the risk factors of repeat percutaneous vascular closure devices for subsequent infectious complications. A 43-year-old male underwent cardiac catheterization and closure with an Angio-Seal (St. Judes Medical, Inc., St. Paul, MN) device. He required a second cardiac catheterization with access gained on the same side as the previous intervention. He developed bacteremia and an infected hematoma with erosion of the femoral artery. The second case involves a 57-year-old male who underwent cardiac catheterization and closure with an Angio-Seal device. He developed a localized infection over the accessed groin site. The overall complication rate of closure devices is 2%, and 0.3% of patients have infectious complications. The high morbidity associated with these complications indicates the need to be able to identify patients who are at increased risk for these complications.