Purpose: In adolescents, the definition and clinical implications of metabolically healthy overweight (MHO) status have not been established. This study aimed to investigate the prevalence of MHO according to its most widespread definition, which is based on metabolic syndrome (MS), and to explore further metabolic indicators such as Homeostatic Model Assessment of Insulin Resistance, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and C-reactive protein levels, together with metabolic health predictors in a sample of adolescents attending a pediatric obesity clinic. Methods: Data from 487 adolescents categorized as overweight (52.6% females, 88.1% white), with a mean body mass index (BMI) z-score of 2.74 (±1.07 standard deviation [SD]), and a mean age of 14.4 years (±2.2 SD) were cross-sectionally analyzed. From this original sample, a subsample of 176 adolescents underwent a second assessment at 12 (±6 SD) months for longitudinal analysis. Results: From the 487 adolescents originally analyzed, 200 (41.1%) were categorized as MHO, but only 93 (19.1%) had none of the metabolic indicators considered in this study. According to longitudinal analysis, 30 of the 68 adolescents (44%) categorized as MHO at baseline became non-MHO over time. BMI z-score was the best predictor of metabolic health both in cross-sectional and longitudinal analyses. Increased BMI z-score reduced the odds of being categorized as MHO (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4–0.9; P=.008) and increased the odds of having hypertension (OR 2.1, 95% CI: 1.4–3.3, P=0.001), insulin resistance (OR, 2.4; 95% CI, 1.4–4.1, P=0.001), or a proinflammatory state (OR, 1.2; 95% CI, 1.1–1.3, P=0.002). Conclusion Diagnosis of MHO should not be exclusively based on MS parameters, and other metabolic indicators should be considered. Adolescents categorized as overweight should participate in weight-management lifestyle interventions regardless of their metabolic health phenotype.