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Background: The first‐generation BTK inhibitor ibrutinib is a standard‐of‐care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. Methods: This study used 2013–2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. Results: The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow‐up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient‐months for all discontinuers and 32.9 per 1000 patient‐months for non‐discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient‐months compared with non‐discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). Conclusion: In this first real‐world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib‐related AEs and/or new treatments to improve real‐world outcomes in patients with CLL. [ABSTRACT FROM AUTHOR]