A successfully treated case of a spontaneous aortic thrombosis in a neonate is described as an illustration of the advantages of using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for anticoagulation therapy. A 5-day-old neonate presented with an abdominal aortic thrombosis detected by echocardiography. Intravenous UFH was commenced following thrombectomy. Poor venous access made monitoring the anticoagulation therapy problematic. Subcutaneous LMWH was substituted for UFH. It requires substantially less monitoring and no intravenous access, has fewer side effects, and allows for much earlier discharge from the hospital. Extensive investigation for a hypercoagulable state revealed no definite cause for the thrombus. The findings of homozygosity for a methylene tetrahydrofolate reductase (MTHFR) mutation and a mildly elevated homocysteine level are interesting but unlikely to account for the thrombotic event in this case. Anticoagulation with LMWH proved effective and more convenient than using UFH.