We report for the first time, a premature infant with multiple intracardiac thrombi and sepsis, who was heterozygous for the G20210A prothrombin gene variant. Anticoagulant treatment with low molecular weight heparin resulted in the complete disappearance of the thrombi. It may be suggested that prothrombin gene variant associated with sepsis, respiratory distress syndrome, and perinatal asphyxia, as well as other thrombophilic disorders, could be a risk factor for the development of neonatal thrombus.