Valvular heart disease is prevalent and represents a significant contributor to cardiac morbidity and mortality. Several options for valve replacement exist, including surgical replacement and transcatheter valve implantation. Prosthetic valves lead to increased risk of thromboembolic disease; therefore, antithrombotic therapy after valve replacement is indicated. For patients with mechanical prostheses, indefinite vitamin K antagonist and antiplatelet therapy are the mainstays of treatment. There is no consensus regarding optimal antithrombotic therapy after bioprosthetic valve replacement, although vitamin K antagonist therapy of varying duration in addition to antiplatelet therapy is recommended by guidelines. Dual-antiplatelet therapy is commonly used after transcatheter valve implantation; however, alternative antithrombotic regimens are being studied. Further studies are needed to identify the optimal regimen, intensity, and duration of antithrombotic therapy after surgical bioprosthetic valve replacement and transcatheter valve implantation.