Although many individuals are able to achieve weight loss, maintaining this loss over time is challenging. We aimed to study whether genetic predisposition to general or abdominal obesity predicts weight regain after weight loss. We examined the associations between genetic risk scores for higher BMI and higher waist-to-hip ratio adjusted for BMI (WHR_adjBMI) with changes in weight and waist circumference up to 3 years after a 1-year weight loss program in participants (n = 822 women, n = 593 men) from the Look AHEAD (Action for Health in Diabe-tes) study who had lost ≥3% of their initial weight. Genetic predisposition to higher BMI or WHR_adjBMI was not associated with weight regain after weight loss. How-ever, the WHR_adjBMI genetic score did predict an increase in waist circumference independent of weight change. To conclude, a genetic predisposition to higher WHR_adjBMI predicts an increase in abdominal obesity after weight loss, whereas genetic predisposition to higher BMI is not predictive of weight regain. These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain.