OBJECTIVE: Insulin resistance (IR) is central to cardiometabolic risk in obesity, but the clinical utility of IR indices may vary by age. We compared homeostasis model assessment for insulin resistance (HOMA-IR) and metabolic score for insulin resistance (METS-IR) across age groups in obese adults and examined comorbidity burden and discriminatory performance for type 2 diabetes mellitus (T2DM) and hypertension (HT). SUBJECTS AND METHODS: This retrospective, single-center study included adults with a BMI ≥ 30 kg/m2 (n = 481) across four age strata (18-40, 40-65, 65-75, and ≥75 years). Spearman correlation assessed the association between HOMA-IR and METS-IR. Comorbidity burden (0-3 chronic conditions) was modeled using ordinal logistic regression per 1-SD increase in z-scores, adjusted for age, sex, and BMI. Receiver operating characteristic analysis and multivariable logistic regression assessed T2DM and HT. RESULTS: HOMA-IR and METS-IR were moderately correlated (ρ = 0.342 and p < 0.001, respectively). METS-IR was associated with comorbidity burden (adjusted odds ratio [OR] 1.84; 95% confidence interval [CI] 1.26-2.69; p < 0.01), whereas HOMA-IR was not (OR 1.12; 95% CI 0.92-1.36; p = 0.256). Discriminatory performance was limited for T2DM (area under curve [AUC] 0.500 vs. 0.537) and HT (AUC 0.471 vs. 0.519). METS-IR remained associated with T2DM (OR 2.51; 95% CI 1.60-3.93; p < 0.001) and HT (OR 1.81; 95% CI 1.13-2.91; p < 0.05). CONCLUSION: In obese adults, METS-IR demonstrated a stronger association with comorbidity burden than HOMA-IR. However, because both indices showed limited discriminatory performance for T2DM and HT, they should not be used as standalone tools for treatment guidance or diagnostic classification. Rather, they should be interpreted alongside age, clinical, and biochemical findings, as isolated use may be misleading and fail to identify disease in specific patient subgroups.