OBJECTIVE: Overweight and obese individuals are encouraged to lose 5-10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes. RESULTS: The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% (means ± SD 7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA₁c (odds ratio 3.52 95% CI 2.81-4.40), a 5-mmHg decrease in diastolic blood pressure (1.48 1.20-1.82), a 5-mmHg decrease in systolic blood pressure (1.56 1.27-1.91), a 5 mg/dL increase in HDL cholesterol (1.69 1.37-2.07), and a 40 mg/dL decrease in triglycerides (2.20 1.71-2.83). The odds of clinically significant improvements in most risk factors were even greater in those who lost 10-15% of their body weight. CONCLUSIONS: Modest weight losses of 5 to <10% were associated with significant improvements in CVD risk factors at 1 year, but larger weight losses had greater benefits.