Currently, there are no fully developed interventional approaches for the treatment of tricuspid regurgitation (TR). The aim of this study was to evaluate the feasibility of orthotopic interventional placement of a biological prosthetic valve in the tricuspid position by inserting, with a transvenous approach, a self-expandable valve-bearing stent into the right atrium. Based on findings of computerized tomography (CT), a model of the porcine right heart was obtained. A self-expanding vascular endoprosthesis, carrying a prosthetic heart valve, was reshaped to fit the superior vena cava and the tricuspid annulus. Fenestrations were created to allow blood flow from the inferior vena cava and coronary sinus. This new device ("tricuspid endoprosthesis": TE) was implanted operatively into the superior vena cava, right atrium, and tricuspid annulus in six pigs. CT demonstrated proper fitting of the device, and echocardiography demonstrated correct positioning and function of the TE. Five animals were successfully weaned from cardiopulmonary bypass. Autopsy confirmed correct positioning of the TE without major trauma to surrounding tissues. These findings demonstrate a complete interventional approach for treating TR.