The present invention features an all-in-one system for vascular access and closure. In particular, this invention features systems and methods for forming holes in blood vessels and rapidly closing these vessel holes using an all-in-one system. For example, an arterial access and closure port system is disclosed herein to provide fail-safe percutaneous entry and exit into any artery, particularly useful for high flow and high pressure arteries such as the carotid artery. The present invention is a single system that forms and closes vascular holes and can be used for percutaneous arterial access with interventional radiology, interventional cardiology, neuro-intervention, endovascular surgery, and endovascular neurosurgery.