Abstract Background Although obesity is a well-established risk factor for atrial fibrillation (AF), the relationship between weight change and the risk of AF remains controversial. Furthermore, the extent to which obesity-associated AF risk is mediated by cardiac remodeling is unclear. Purpose We aimed to evaluate the impacts of obesity and weight change on the risk of atrial fibrillation, and the role of cardiac remodeling in obesity-AF association. Methods This is a population-based prospective cohort of UK Biobank participants recruited from 2006 to 2010. A total of 490,969 participants and 19,634 participants were included for BMI and BMI change analysis, respectively. Body mass index (BMI) was assessed at baseline and follow-up assessment (2012-2013). Cardiovascular measurements were derived from cardiovascular magnetic resonance. Cox proportional hazard models were used to assess the associations of obesity and change in BMI with AF. The nonlinear associations of BMI and BMI change with AF were tested using a restricted cubic spine (RCS). Mediation analysis was conducted to quantify the role of cardiac remodeling in the association between obesity and AF. Results Among the 490,969 participants included (mean age: 56.4 ± 8.1 years, 54.9% women), 33,297 incident AF cases were observed during a median follow-up of 14.0 years. Overweight (hazard ratio [HR], 1.12, 95% confidence interval [CI] 1.09-1.15, P < 0.001) and obesity (1.73, 1.68-1.78, P < 0.001) significantly increased the risk of AF, particularly in men, those with age < 60 years and low genetic risk. During a median follow-up of 4.43 years, 1,217 (6.2%) participants experienced > 2% BMI loss per year and 1,318 (6.7%) participants experienced > 2% BMI gain per year. Compared to stable BMI, BMI loss was associated with a lower risk of AF (0.75, 0.57-0.99, P = 0.039). In addition, we found that BMI loss from obesity to overweight was associated with a reduced risk of AF (0.74, 0.54-1.02, P = 0.069) compared with maintaining baseline BMI category. Participants with stable obesity had a higher risk of AF (1.81, 1.52-2.16, P < 0.001) than those with stable normal weight. In addition, RCS indicated BMI had a J-shaped association with AF while BMI change had a linear association with AF. Mediation analyses revealed that left ventricular myocardial mass, left atrial maximum volume, and left atrial minimum volume were the three strongest mediating factors between obesity and AF, with a mediated proportion of 85.28%, 64.43%, and 55.89% of the total effect, respectively. Conclusion BMI decrease over 2% per year was associated with a lower risk of AF, especially in those changing from obesity to overweight. Left ventricular myocardial mass plays a central role in mediating obesity-related AF. Our findings support weight management at the population level to mitigate the growing epidemic of AF and ways targeting left ventricular myocardial mass are waiting to be further explored.Associations of BMI, BMI change with AFThe mediating role of cardiac remodeling