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Cigarette smoking and atrial fibrillation (AF) are associated with impaired brain health. We investigated the association between smoking habits and brain lesions and volume in patients with AF. In patients with AF from a multicenter cohort study, we assessed smoking status (never, ex-, active), number of cigarettes smoked per day, smoking duration (years), pack-years, and time since smoking cessation. On brain magnetic resonance imaging, the prevalence and volumes of white matter lesions (WML) and small noncortical infarcts, and the volumes of gray matter and white matter were evaluated. Logistic and linear regression analyses were used to analyze the association between smoking habits and brain lesions and volumes. A total of 1,728 patients were enrolled (mean age 72.6 years, 27.5% female); 7.5% were active smokers; 48.5% were ex-smokers, and 44% had never smoked. We found linear associations of number of cigarettes smoked per day, pack-years, and older age at smoking cessation with reduced gray matter volume (p for linear trend <0.01, 0.02, and 0.01, respectively). Patients with a smoking duration in the second and third tertile had a greater risk for WML Fazekas ≥2 (odds ratio 1.86, 95% confidence interval 1.29 to 2.69, p <0.01 and 1.47 [1.02 to 2.12], p = 0.04), and exhibited larger WML volumes. Patients who had stopped smoking ≥16 years before enrollment were less likely to have small noncortical infarcts (odds ratio 0.46, 0.25 to 0.88, p = 0.02) and had smaller WML volumes (β: -0.451 mm 3 , -0.8 to -0.11, p = 0.01). In conclusion, smoking intensity and time since smoking cessation were associated with the presence and volume of brain lesions and with brain volumes in patients with AF., Competing Interests: Declaration of competing interest Dr. Aeschbacher received a speaker fee from Roche Diagnostics. Dr. Bonati reports personal fees and nonfinancial support from Amgen, grants from AstraZeneca, personal fees and nonfinancial support from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Claret Medical, grants from Swiss National Science Foundation, grants from University of Basel, and grants from Swiss Heart Foundation, outside the submitted work. Dr. Conen received consulting fees from Roche Diagnostics; and speaker fees from Servier and Bristol-Myers Squibb/Pfizer (New York, New York), all outside the current work. Dr. Krisai reports speaker fees from BMS/Pfizer and research grants from the Swiss National Science Foundation (SNSF), the Swiss Heart Foundation (SHS), the Foundation for Cardiovascular Research Basel, and the Machaon Foundation. Dr. Kühne reports personal fees from Bayer, Böhringer Ingelheim, Pfizer BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson&Johnson, and Roche; and grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo. Dr. Müller received fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, and Novartis; and is a consultant for Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik (all outside the current work). Dr. Osswald received research grants from the SNSF, the SHS, the Foundation for Cardiovascular Research Basel, and Roche; and received educational and speaker office grants from Roche, Bayer, Novartis, Sanofi AstraZeneca, Daiichi Sankyo, and Pfizer. Dr. Reichlin received research grants from the SNSF, the SHF, the European Union [Eurostars 9,799–ALVALE), and the Cardiovascular Research Foundation Basel, all for work outside the submitted study; received speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense‐Webster, Biotronik, Boston‐Scientific, Daiichi Sankyo, Medtronic (Abbott), Pfizer‐BMS, and Roche, all for work outside the submitted study; and received support for his institution's fellowship program from Abbott/SJM, Biosense‐Webster, Biotronik‐Scientific, and Medtronic, for work outside the submitted study. Dr. Rodondi received a grant from the SHF. Dr. Zuern received a travel grant from Cardiomatics., (Copyright © 2024 Elsevier Inc. All rights reserved.)