We describe an unusual and interesting case of a full-term infant presenting at 7 days of life with HSV pneumonitis and a tricuspid valve thrombus ultimately requiring extracorporeal membrane oxygenation. The infant subsequently developed a pulmonary embolus. The infant was found to be heterozygous for the prothrombin G20210A mutation and homozygous for the methylenetetrahydrofolate reductase C667T mutation. The patient was treated with low molecular weight heparin for a total of 3 months and has not had a recurrent thrombosis. This case illustrates that a combination of congenital and acquired thrombophilic risk factors can contribute to a significant thrombotic event.