The prevalence of radiation-associated cardiac disease is increasing due to prolonged survival following mediastinal irradiation. Side effects of radiation include pericarditis, accelerated coronary artery disease, myocardial fibrosis and valvular injury. We evaluated the cases of three young patients with evidence of significant valvular disease following mediastinal irradiation. One patient underwent the first reported successful aortic and mitral valve replacement for radiation-associated valvular disease (RAVD) as well as concurrent coronary artery revascularization. A review of the literature revealed 35 reported cases of RAVD, with only one successful case of valve replacement that was limited to the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal irradiation compared with 16.5 years for symptomatic patients, emphasizing that long-term follow-up is important for patients receiving mediastinal irradiation. This study defines a continuum of valvular disease following radiation that begins with mild asymptomatic valvular thickening and progresses to severe valvular fibrosis with hemodynamic compromise requiring surgical intervention.