Background and Aim: TL1A (TNFSF15) is a major Crohn's disease (CD) susceptibility gene, especially in the East Asian population, and is also known to be associated with some clinical phenotypes, such as stricturing and penetrating behavior. This study aims to investigate the association between TL1A genotype and the long-term therapeutic outcomes of infliximab and adalimumab in Japanese CD patients. Methods: We investigated 119 biologic-naïve CD patients treated with infliximab or adalimumab. TL1A -358C/T (rs6478109) was genotyped as a tag single nucleotide polymorphism (SNP) for CD risk or nonrisk haplotype of TL1A (the -358C allele is a risk allele for CD development). We compared the long-term therapeutic outcomes of anti-tumor necrosis factor (TNF) antibodies between the TL1A -358C/C group and the C/T+T/T group. Results: Sixty-nine cases (58.0%) were homozygous for the risk allele (TL1A -358C/C group), and 50 cases (42.0%) were heterozygous for the risk allele or homozygous for the protective allele (TL1A -358C/T+T/T group). No significant differences were found in the cumulative retention rates and the relapse-free survival between the TL1A genotypes. However, the surgery-free survival was significantly lower in the TL1A -358C/C group than in the C/T+T/T group (log-rank test, P < 0.05). Multivariate analysis showed that TL1A -358C/C was identified as an independent risk factor for surgery (hazard ratio, 4.67; 95% confidence interval, 1.39-22.1; P = 0.025). Conclusion: An association was found between the TL1A genotype and the therapeutic outcomes of anti-TNF therapy. Our data indicate that the design of customized therapy with anti-TNF antibodies using TL1A genomic information could be effective in the future.