Devices, systems and methods for transvascular interstitial interventions, including transvascular, catheter based vascular bypass, transmyocardial revascularization, bypass grafting of blood vessels, and interstitial surgical/interventional procedures wherein a catheter is advanced translumenally through the vasculature to a desired location and an operative instrument is passed through the wall of a blood vessel and to a target location (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.