This invention is devices, systems and methods for trans-vascular interstitial interventions, including trans-vascular, catheter based vascular bypass, transmyocardial re-vascularization, bypass grafting of blood vessels, and interstitial surgical/interventional procedures wherein a catheter is advanced trans-lumenal through the vasculature (2) to a desired location (OB) and an operative instrument (5) is passed through the wall (2) of a blood vessel (2) and to a target location (3) (e.g., another blood vessel, an organ, a tumor, another anatomical structure) such that one or more operative devices may be advanced to the target location to perform the desired operative or interventional procedure.