Aims Limited causal evidence is available on the relationship between body mass index (BMI) and atrial fibrillation (AF) progression. Sex differences have been noted and may be relevant for AF progression. We investigated the association between the BMI Genetic Risk Score (GRS) and AF progression in men and women of the Groningen Genetic Atrial Fibrillation (GGAF) cohort. Methods and results The GGAF cohort (n = 2207) is a composite of 5 prospective cohorts with individuals of European ancestry. AF patients with genetic information, with at least 12 months follow-up and AF progression data were included. AF progression was defined as progression from paroxysmal to persistent/permanent AF, or persistent to permanent AF. A BMI GRS was constructed of genetic variants associated with BMI. Univariate and multivariate Cox proportional hazard regression analyses were performed in the total population and in men and women, separately. During a median follow-up of 34 [interquartile range 19–48] months 630 AF patients (mean age 62±11, 36% women, BMI of 28±5) were analyzed, and men and women developed similar AF progression rates (respectively 6.5% versus 6.1%). The BMI GRS was not associated with AF progression either as a continuous variable or in tertiles in the overall population. However, the BMI GRS was associated with the tertile of the highest BMI GRS in women (n = 225), also after multivariable adjustments of clinical risk factors (Hazard ratio 2.611 (95% confidence interval 1.151–5.924) p = 0.022). Conclusions Genetically-determined BMI is only associated with women at risk of AF progression. The results may be supporting evidence for a causal link between observed BMI and AF progression in women. We emphasize the need for further investigation of genetically determined BMI and observed BMI to optimize AF management in women with increased risk for AF progression.