PURPOSE: Inflammatory Bowel Disease (IBD) predominantly affects younger individuals, but emerging data indicates a shift toward older populations. Elderly-onset IBD (diagnosed at 60 years or older) differs from younger-onset IBD, presenting with atypical symptoms and higher risks of infections and malignancies. However, drug persistence is underexplored in the elderly IBD group, warranting further investigation to optimize treatment strategies for this demographic. PATIENTS AND METHODS: This retrospective cohort study included IBD patients receiving advanced therapies at the Chang Gung IBD Center from October 2017 to September 2023. Patients were stratified into two groups: elderly-onset (>/=60 years) and control (<60 years). We compared one-year persistence of advanced therapies, opportunistic infections, IBD-related admissions, complications, surgeries, and acute flare-ups between the groups. Specifically, we analyzed the one-year persistence of various advanced therapies within the elderly-onset cohort. RESULTS: The study included 511 IBD patients, 107 of whom were elderly-onset. Elderly-onset patients had a higher body mass index, a higher proportion of ulcerative colitis, fewer smokers, and lower levels of white blood cells, hemoglobin, and albumin. Differences were noted in Montreal classifications and a higher use of Vedolizumab. Clinical outcomes, including steroid-free remission rates, one-year therapy persistence, infections, complications, surgeries, and flare-ups, were comparable between groups. In Crohn's disease (CD), Infliximab and Ustekinumab exhibited higher one-year persistence. Predictors of one-year therapy persistence included Montreal L1 (OR: 6.722; 95% CI: 1.296-34.852; P=0.023), Ustekinumab use (OR: 5.672; 95% CI: 1.138-28.267; P=0.034), and hemoglobin level (OR: 1.612; 95% CI: 1.210-2.147; P=0.001) with an optimal cutoff of 11.65 g/dL. CONCLUSION: Elderly-onset IBD patients display unique clinical characteristics and therapy persistence, particularly in CD, highlighting the necessity for customized therapeutic strategies.