Abstract Context It is largely unknown whether regional fat accumulation is associated with risk of cardiovascular disease (CVD) and mortality among individuals with type 2 diabetes (T2D), who often exhibit changes in relative fat distribution and have increased CVD risk. Objective To prospectively examine the association between regional body fat and risk of CVD in individuals with T2D and to determine whether the associations are independentof traditional measures of obesity. Methods The main analysis included 21 472 participants with T2D from the UK Biobank. Regional body fat was measured by bioelectric impedance assessment. Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Results Over a median of 7.7 years of follow-up, 3976 CVD events occurred. After multivariable adjustment, upper and lower body fat were independently and oppositely associated with CVD risk among patients with T2D. Higher arm fat percentage was linearly associated with increased CVD risk (Pnonlinear > .05), while higher trunk fat percentage was nonlinearly associated with increased CVD risk (Pnonlinear < .05). In contrast, higher leg fat percentage was nonlinearly associated with lower CVD risk (Pnonlinear < .05). When comparing extreme quartiles, the multivariable-adjusted HR (95% CI) of CVD was 0.72 (0.58-0.90) for leg fat percentage, 1.63 (1.29-2.05) for arm fat percentage, and 1.27 (1.06-1.52) for trunk fat percentage. Similar patterns of associations were observed for all-cause and CVD mortality. In addition, leg fat percentage, but not other regional fat percentage, was associated with CVD risk independently of traditional measures of obesity. Conclusion Among people with T2D, arm fat and trunk fat were positively, whereas leg fat was inversely, associated with the risk of CVD and mortality. These findings highlight the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among individuals with T2D.