© 2018 Mayo Foundation for Medical Education and Research More than two-thirds of American adults are overweight or obese, with many attempting to lose weight to avoid adverse health outcomes and improve well-being. Achieving long-term weight loss (LTWL) success, defined as reaching at least a 5% to 10% weight loss goal, is challenging, yet important for overall metabolic health. It is currently unclear whether achieving higher thresholds of LTWL is associated with improved health. Therefore, the purpose of this study was to examine the association between LTWL thresholds (5%-9.9%, 10%-14.9%, 15%-19.9%, ≥20%) and metabolic health (metabolic syndrome and metabolic risk z score) among 7670 US adult respondents to the National Health and Nutrition Examination Survey (2007-2014) who were overweight or obese (past or present), were not underweight in the past year, not pregnant, and attempting to lose or maintain weight. A subsample of 3362 participants was used in the analysis of the metabolic risk z score. Multivariable regression models were constructed adjusting for covariates. Results indicate that the lowest and the 2 highest LTWL thresholds were related to lower odds for metabolic syndrome; for example, greater than or equal to 20% LTWL (odds ratio=0.52; 95% CI, 0.23-0.44; P<.001). All LTWL thresholds were significantly associated with the metabolic risk z score, with the largest effect among the 2 highest LTWL thresholds, that is, 15% to 19.9% LTWL (β=−0.45; 95% CI, −0.54 to −0.36; P<.001) and greater than or equal to 20% LTWL (β=−0.35; 95% CI, −0.53 to −0.17; P<.001). In conclusion, although achieving the currently recommended LTWL target was related to improved metabolic health, the 15% LTWL threshold was associated with more favorable outcomes.