Abstract Background There is limited evidence for the significance of the combination of waist circumference (WC), as a surrogate marker of central obesity, with body mass index (BMI) for predicting the risk of atrial fibrillation (AF). Furthermore, the additive value of the burden of BMI and WC cumulated over time on AF risk has not been reported. Purpose We sought to investigate the effect of cumulative burden of BMI, WC, and their combinations on the risk of AF using health check-up data from the Korean National Health Insurance Service. Methods This study included subjects aged >20 years who underwent four times of annual national health check-ups serially during 2009 to 2013, excluding those with a previous history of AF. The 4-year cumulative burden of BMI and WC was represented as burden-score calculated by the summation of BMI score (BMI 18.5–23 kg/m2, score 0; BMI 23–25 kg/m2, score 1; BMI ≥25 kg/m2, score 2) and WC score (WC <90 cm for men or <85 cm for women, score 0; WC ≥90 cm for men or ≥85 cm for women, score 1) at each year of health check-up. Newly developed AF was identified using claims data during a median follow-up of 5.2 years. AF risk was evaluated according to the burden of BMI, WC, and their combinations. A multivariate Cox regression model was used to adjust for baseline differences. Results Of 3,726,172 subjects (mean age 44.5±11.1, men 69.5%) enrolled, 27% had BMI burden-score of zero, while 23% had maximal burden-score of 8. For WC, 71% had zero burden-score and 7% had the highest burden-score of 4. Compared to the zero burden-score, maximal burden-score of BMI mildly increased the risk of AF, whereas the risk of AF predominantly increased in the group of maximal burden-score of WC. The different burdens of BMI in the same WC burden group did not significantly affect the risk of AF. Adjusted HR of each BMI burden-score (BMI burden zero as a reference) ranged from 1.01 to 1.12 in the group with WC burden-score zero, 0.84 to 1.06 in WC burden-score 1, 0.84 to 1.19 in WC burden-score 2, 0.59 to 0.83 in WC burden-score 3, and 0.62 to 1.55 in WC burden-score 4 without statistical significance. In contrast, high WC burden-score further increased the risk of AF even in groups with moderate to high burden of BMI (adjusted HR of maximal WC burden versus zero burden 1.97 [1.49–2.59] in the group with BMI burden-score 4; 1.66 [1.23–2.24] in BMI burden-score 5; 1.49 [1.16–1.91] in BMI burden-score 6; 1.43 [1.18–1.73] in BMI burden-score 7; and 1.49 [1.38–1.60] in BMI burden-score 8). Conclusions The 4-year cumulative burden of WC was a stronger determinant of future AF risk than BMI burden. Particularly in middle-ranged BMI burden groups that include persistently overweight but not obese population, high burden of WC substantially increased the risk of AF. The strategy of active surveillance for AF and comprehensive management of lifestyle and risk factors should focus on high-risk populations determined by the burden of WC. Funding Acknowledgement Type of funding sources: None.