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To examine the association between genetic predisposition to type 2 diabetes (T2D) and risk of cardiovascular disease (CVD) among patients with T2D.The current study included 1,012 men and 1,310 women with T2D from the Health Professionals Follow-up Study and Nurses’ Health Study, including 677 patients with CVD and 1,645 non-CVD control subjects. A genetic predisposition score (GPS) was calculated on the basis of 36 established independent diabetes-predisposing variants.Each additional diabetes-risk allele in the GPS was associated with a 3% increased risk of CVD (odds ratio [OR] 1.03 [95% CI 1.00–1.06]). The OR was 1.47 (1.11–1.95) for CVD risk by comparing extreme quartiles of the GPS (P for trend = 0.01). We also found that the GPS was positively associated with hemoglobin A1c levels (P = 0.009).Genetic predisposition to T2D is associated with an increased risk of cardiovascular complications in patients with T2D.