Objective: To compare the safety and efficacy of warfarin plus aspirin versus aspirin alone for the treatment of children with giant coronary artery aneurysm (CAA) secondary to Kawasaki disease (KD). Methods: We searched the PubMed, EMBASE, Cochrane Library, CNKI, WANFAN and VIP databases. We selected case-controlled trials of warfarin plus aspirin versus aspirin alone for the treatment of children with giant CAA secondary to KD. Results: Six retrospective studies met our inclusion criteria. There was no significant difference between the warfarin plus aspirin and aspirin alone groups in the rate of CAA regression (OR 1.38, 95% CI 0.52-3.68, p = 0.52) or the incidence of persistent CAA (OR 2.34, 95% CI 0.16-33.50, p = 0.53), coronary artery stenosis (OR 0.55, 95% CI 0.18-1.72, p = 0.30) or thrombus formation (OR 0.50, 95% CI 0.15-1.69, p = 0.26). There was evidence that warfarin plus aspirin reduced the incidence of coronary artery occlusion (OR 0.08, 95% CI 0.02-0.29, p < 0.0001), cardiac infarction (OR 0.27, 95% CI 0.11-0.63, p = 0.003) and death (OR 0.18, 95% CI 0.04-0.88, p = 0.03). Conclusion: Warfarin plus aspirin therapy reduced the incidence of occlusion, cardiac infarction and death in children with giant CAA secondary to KD.