OBJECTIVE: The aim of this study was to assess the relative urate-lowering efficacy and safety of febuxostat and allopurinol in hyperuricemic patients with or without gout. METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of febuxostat compared to allopurinol or placebo in hyperuricemic patients with/without gout were included in this Bayesian network meta-analysis. RESULTS: Eight RCTs including 4,099 patients met the inclusion criteria. The number of subjects achieving a serum urate (sUA) level <6.0 mg/dL was significantly higher in the febuxostat 120 mg and 80 mg groups than in the allopurinol (100 to 300 mg) group (odds ratio [OR] 7.17, 95% credible interval [CrI] 3.86 to 14.09; OR 3.49, 95% CrI 1.97 to 5.91, respectively). However, achievement of the target sUA level was comparable between febuxostat 40 mg and allopurinol. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that febuxostat 120 mg had the highest probability of being the best treatment for achieving the target sUA (SUCRA=0.9973), followed by febuxostat 80 mg (SUCRA=0.752), febuxostat 40 mg (SUCRA=0.4289), allopurinol (SUCRA=0.3217), and placebo (SUCRA=0). In contrast, no significant difference in safety based on the number of withdrawals due to adverse events was observed among the 5 interventions. CONCLUSION: Febuxostat 80 mg and 120 mg were more efficacious than allopurinol (100 to 300 mg), and febuxostat 40 mg and allopurinol were comparable in urate-lowering efficacy. The safety of febuxostat at all doses was comparable with that of allopurinol.