Tricuspid valve replacement for infective endocarditis (TVE) in intravenous drug abusers (IVDAs) may pose special clinical challenges, since mechanical prostheses require lifelong anticoagulation therapy, and bioprostheses degenerate over time, especially in young patients. The Inspiris aortic bioprosthesis has been designed to reduce the rate of structural valve deterioration (SVD) and to improve durability. We describe three IVDAs with TVE undergoing tricuspid valve replacement with an inverted Inspiris valve, and discuss the potential advantages of this approach.