The safety of newer xanthine oxidase inhibitor-febuxostat comparing to allopurinol remains unclear. To compare the risks of allopurinol- and febuxostat-hypersensitivity and cardiovascular diseases (CVD) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012-2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users. The overall incidence of febuxostat-hypersensitivity was significantly lower than allopurinol-hypersensitivity (0.2v.s.2.7 per 1000 new users, P<0.001). There were 33 allopurinol-hypersensitivity (including 18 severe cutaneous adverse drug reactions) and only one patient developed febuxostat-maculopapular exanthema. Moreover, febuxostat was not statistically increased risk of CVD (HR,1.16; P=0.152) and related death (HR,1.49; P=0.496) compared to allopurinol. The result of meta-analysis also showed consistent result. In conclusion, the incidence and severity of febuxostat-hypersensitivity are lower than with allopurinol. Febuxostat didn't show an increased risk of CVD and related death. This article is protected by copyright. All rights reserved.