Introduction: The 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults recommended weight loss for obese adults in order to reduce their cardiovascular disease (CVD) risk. However, not all obese adults develop CVD and approximately 17% of obese Americans in the 1999-2004 NHANES were metabolically healthy. The absence of abnormal CVD risk factors in this subgroup of obese adults indicates that some individuals are resistant to excess adiposity and positive energy balance, and raises the question of whether all obese adults should be recommended for weight loss treatment. We know of no study that has examined whether metabolically healthy obese (MHO) adults respond to weight changes the same way as metabolically healthy normal weight adults (MHNW). Also, no study has compared the effects of weight loss, weight maintenance and weight gain on CVD risk factors in MHO adults. Hypothesis: We hypothesized that the effects of weight change would be different in MHNW and MHO adults, with MHO adults having less stable risk factors, and that weight loss has a protective effect on CVD risk factors in the MHO compared to weight maintenance and weight gain. Methods: Data were from 2,710 MHO and MHNW participants in the Atherosclerosis Risk in Communities (ARIC) study. Four examinations yielded 4,541 observations over sequential 3-year intervals. Metabolically healthy was defined as absence of all components of metabolic syndrome, excluding waist circumference, at the beginning of a 3-year interval. Mixed effect models were applied to individually compare changes in five CVD risk factors (systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and glucose) in MHO and MHNW adults within 3 weight change categories (<3% weight loss, weight maintenance (±3%) and >3% weight gain). Results: Weight loss was associated with small or no changes in the five CVD risk factors in both MHO and MHNW adults. Weight maintenance was associated with larger increases in MHO compared to MHNW adults in triglycerides (mean ± standard error: 10.0±1.7 vs. 6.5±1.0 mg/dL) and glucose (1.7±0.4 vs. 0.9±0.2 mg/dL). Weight gain was associated with larger increases in systolic (8.6±0.6 vs. 6.2±0.4 mmHg) and diastolic (3.9±0.4 vs. 2.5±0.3 mmHg) blood pressure, triglycerides (22.0±1.8 vs. 16.0±1.1 mg/dL) and glucose (4.9±0.4 vs. 1.9±0.3 mg/dL) among the MHO compared to the MHNW. MHO weight losers experienced more favorable changes in the five CVD risk factors compared to MHO weight maintainers (p<0.04) or gainers (p<0.0001). Conclusions: We showed that compared to MHNW, MHO adults experienced similar changes in CVD risk factors with weight loss and larger increases with weight maintenance and gain. Our study supports the 2013 Guideline that primary health care providers should recommend weight loss treatment for MHO patients.