Background: Inflammatory bowel disease (IBD) presents unique challenges in elderly patients due to comorbidities and treatment-related risks. Objectives: This study evaluates ustekinumab (UST) and vedolizumab (VDZ) efficacy and safety in elderly Crohn's disease (CD) patients. Design: A retrospective cohort study at a tertiary medical center. Methods: CD patients aged >= 60 years (elderly) treated with UST, compared to non-elderly (<60 years) patients treated with UST and elderly patients treated with VDZ. Clinical response was evaluated using the Harvey-Bradshaw index (HBI) and clinical biomarkers, alongside monitoring steroid use, hospitalization rates, treatment persistence, and surgical interventions. Results: The study included 166 CD patients: 32 elderly and 65 non-elderly patients treated with UST, and 69 elderly patients treated with VDZ. The mean duration of follow-up was 10.8 +/- 2.8 months in the non-elderly group, 9.97 +/- 3.28 months in the elderly UST group, and 10.0 +/- 3.29 months in the VDZ group. Elderly UST patients were more likely to receive corticosteroids at initiation than non-elderly UST patients (44% vs 14%, p = 0.001). At 12 months, clinical response rates did not significantly differ between elderly and non-elderly UST groups, respectively (48% vs 40%, p = 0.5). However, elderly UST patients exhibited higher hospitalization rates over time compared to non-elderly UST patients (6-month: 19% vs 6.2%, p = 0.077; 12-month: 19% vs 4.6%, p = 0.055; log-rank p = 0.004). No significant differences were observed in clinical response and remission rates between elderly UST and elderly VDZ patients at 6 and 12 months. At 6 months, a higher hospitalization rate was observed in the UST group (19% vs 4.3% p = 0.027), but this difference did not persist over time. Conclusion: UST and VDZ are effective and safe treatments for elderly CD patients, despite higher hospitalization rates compared to non-elderly patients, likely due to age-related complications.