Crohn's disease (CD) is an intractable disease that requires long-term treatment. Tumor necrosis factor (TNF) inhibitors have strong efficacy and are widely used for CD treatment. However, a loss of response is one of the issues in long-term TNF therapy. To identify the factors affecting the efficacy of long-term CD treatment with TNF inhibitors, we conducted a retrospective study of treatment outcomes and clinical factors using clinical data over a 14-year period. Clinical characteristics and factors for surgery, hospitalization, and TNF inhibitor treatment discontinuation were examined in 219 biologic-naïve patients who were treated with TNF inhibitors at our hospital before October 2014. Treatment persistence rates with no hospitalization, surgery, or dose escalation were 60.7, 25.9, and 17.3% for 1, 5, and 10years, respectively; these rates did not differ between infliximab (IFX) and adalimumab. In patients receiving IFX dose escalation, 1- and 5-year persistence rates were approximately 90.4 and 65.1%, respectively. Previous surgery (OR=1.45, P=0.043) was identified as a risk factor for surgery, male sex (OR=0.70, P=0.044) and previous surgery (OR=1.51, P=0.03) were risk factors for hospitalization, and perianal fistula (OR=1.39, P=0.049) was the risk factor for TNF inhibitor treatment discontinuation. The durability of anti-TNF therapy in CD patients remains a problem, and treatment optimization that includes dose escalation should be carefully examined depending on patient characteristics and the timing of optimization.