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We explored the joint effects of different metabolic obesity phenotypes on all-cause and disease-specific mortality risk among the American population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality outcome data were from mortality files linked to National Death Index record and follow-up information was up to December 31, 2019. 50,013 participants were finally included. Four metabolic obesity phenotypes were defined based on obesity and metabolic status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Population-weighted Cox proportional hazards models were used to explore the all-cause and disease-specific mortality risk of metabolic obesity phenotypes. The all-cause mortality risk of MUO and MUNO was significantly higher than MHNO. MUNO was associated with a significantly increased risk of death from heart disease (HR: 1.40, 95% CI 1.16-1.70), hypertension (HR: 1.68, 95% CI 1.34-2.12), diabetes (HR: 2.29, 95% CI 1.67-3.15), and malignant neoplasms (HR:1.29, 95% CI 1.09-1.53). Metabolic unhealth significantly increased the risk of all-cause mortality, regardless of obesity status. Among individuals with metabolic unhealthy status, obesity significantly reduced the risk of all-cause mortality (HR: 0.91, 95% CI 0.85-0.98). Our study highlights the importance of identifying and characterizing metabolic obesity phenotypes in obese and metabolically abnormal patients, as well as healthy adults. Comprehensive evaluation of obesity and metabolic status is necessary to adopt appropriate interventions and treatment measures and maximize patient benefit., (© 2024. The Author(s).)