Thromboembolic disease in newborn infants is a serious problem. The most important risk factors are iatrogenic factors, including indwelling umbilical catheters or central catheters. Other risk factors include asphyxia, dehydration, sepsis, cardiac disease, respiratory distress syndrome (RDS), disseminated intravascular coagulation, congenital thrombophilia (i.e., protein C or protein S deficiency), maternal diabetes mellitus, and passive transfer of maternal antiphospholipid antibodies. Neonates are more vulnerable to thrombosis than adults due to their reduced fibrinolytic capability. We describe a case of a 1-day-old female newborn with arterial thromboembolism in the lower leg without a central line catheter. The thromboembolismin in this case was associated with RDS. The infant underwent thrombolysis, anticoagulation therapy, and surgical thrombectomy. The leg of the infant was subsequently amputated below the knee. The case is described here with a brief review of relevant literatures.