Subclinical and clinical thrombosis of bioprosthetic cardiac valves is more common than has been previously recognized. We present a unique case of acute thrombosis of a bioprosthetic mitral valve in a 40-year-old female patient undergoing hormonal stimulation as part of in vitro fertilization therapy, who also had concomitant protein C deficiency that was undiagnosed at the time. To the best of our knowledge, this is the first reported case of acute bioprosthetic valve thrombosis in this complex thrombophilic milieu, and suggests the need for increased screening for prothrombotic risk factors in female patients with bioprosthetic valves before they commence gonadotropin stimulation therapy.