Patients with severe coronary artery involvement after Kawasaki disease (KD) require long-term systemic anticoagulation. We sought to compare our experience with thrombotic coronary artery occlusions, safety profile, and degree of coronary artery aneurysm regression in KD patients treated with low molecular weight heparin (LMWH) versus warfarin. Medical records of all KD patients diagnosed between January 1990 and April 2007 were reviewed. Of 1374 KD patients, 38 (3%) received systemic anticoagulation, 25 patients received LMWH from diagnosis onward, 12 of whom were subsequently switched to warfarin, and 13 received warfarin from onset. The frequency of thrombotic coronary artery occlusions was similar between drugs. Severe bleeding was more frequent in patients on warfarin, but minor bleeding was more frequent for patients on LMWH. Patients on warfarin were at greater risk of underanticoagulation or overanticoagulation (defined as achieving an anti-activated factor X level or an international normalized ratio below or above target level) than patients on LMWH (P < 0.05). Maximum coronary artery aneurysm z-scores diminished with time for patients on LMWH (P = 0.03) but not for those on warfarin (P = 0.55). This study suggests that LMWH is a potentially viable alternative for patients, especially young ones, with severe coronary artery involvement after KD.