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Background: Atrial fibrillation (AF) is a recognized adverse consequence associated with all Bruton's tyrosine kinase inhibitors used to treat chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); however, real-world time to discontinuation (TTD) and time to next treatment (TTNT) of CLL/SLL patients with a high baseline AF/stroke risk remain unknown., Materials and Methods: Patients with CLL/SLL from a nationwide electronic health record-derived database (February 12, 2013-January 31, 2021) initiating first-line (1L) or second or later-line (2L+) treatment with ibrutinib or other regimens on or after February 12, 2014 (index date) were analyzed. Kaplan-Meier survival analysis was used to assess TTD and TTNT among all patients, patients with high AF risk (CHARGE-AF risk score ≥10.0%), and patients at high risk of stroke (CHA 2 DS 2 -VASc risk score ≥3 [females] or ≥2 [males])., Results: In 1L/2L+, 2190/1851 patients received ibrutinib and 4388/4135, were treated with other regimens. Median TTD for ibrutinib was similar regardless of AF/stroke-related risk (1L: all patients, 15.7 months; high AF risk, 11.7 months; high stroke risk, 13.7 months; similar results in 2L+). Median TTNT was significantly longer for ibrutinib vs. other regimens (1L: not reached vs. 45.9 months; 2L+: not reached vs. 23.6 months; both P < .05), including among those with high AF/stroke risk. TTNT was similar between all patients and high-risk cohorts in 1L and 2L+ (all P > .05)., Conclusion: This study highlights that elevated baseline AF/stroke-related risk does not adversely impact TTD and TTNT outcomes associated with ibrutinib use. Additionally, TTNT was significantly longer for patients treated with ibrutinib vs. other regimens., Competing Interests: Disclosure A.N. has received consulting fees from Pharmacyclics, Janssen Scientific Affairs, and Epsilon imaging Inc. B.E., A.H., S.L., M-H.L., and P.L. are employees of Analysis Group, Inc., which has provided paid consulting services to Janssen Scientific Affairs, LLC. S.P.F. was an employee of Analysis Group, Inc. at the time the study was conducted. S.P., X.L., and Q.H. are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. M.C. has received research funding from Abbvie, Pharmacyclics, Oncternal, Velosbio, Merck, and Geron. N.A. reports no relevant conflicts of interest related to this work., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)