<p>Approaches to treating tricuspid valve disease are at the forefront of current clinical investigation. Utilization of an established large animal model to evaluate novel valves is required for regulatory approval prior to clinical investigation. Here we present a sheep model of surgical tricuspid valve replacement using a clinically approved surgical prosthesis. Five adult sheep underwent surgical tricuspid valve replacement (STVR) using a Medtronic Mosaic™ prosthesis and were survived for 140&#xa0;days per regulatory guidance. Serial clinical pathology and echocardiography data was collected. At the study endpoint, echocardiography and cardiac catheterization was performed, followed by a comprehensive necropsy. Four animals successfully underwent STVR. Epicardial echocardiography at the time of implantation and terminal procedure confirmed preserved cardiac output and effective orifice area. Serial transthoracic echocardiography showed no sign of valvular regurgitation and comparable functional parameter throughout the postoperative study period. Intracardiac catheterization at the study endpoint confirmed absence of regurgitant flow across the device at rest and under dobutamine induced stress. Gross pathology revealed a well-seated valve with preserved functional integrity and no signs of downstream thromboembolic events. Using a relevant sheep model of STVR, this study demonstrates how detailed follow-up using echocardiography, intracardiac catheterization as well as clinical and gross pathology can yield valuable long-term in vivo data on tricuspid device safety and function.</p>