PURPOSE: Insulin resistance (IR) plays a significant role in the development of obstructive sleep apnea (OSA). The metabolic score for insulin resistance (METS-IR) is a novel method for assessing IR. This study aims to explore the relationship between METS-IR and the risk of OSA. PATIENTS AND METHODS: This cross-sectional study included a total of 8297 subjects from NHANES (National Health and Nutrition Examination Survey) database, as well as 581 patients who underwent sleep monitoring in Renmin Hospital of Wuhan University. Logistic regression, subgroup analysis, and receiver operating characteristic (ROC) curve analysis were employed for evaluation. RESULTS: In the American population, a significant positive association was found between METS-IR and increased risk of OSA. For each unit increase in METS-IR, the risk of OSA increased by 4.4% (OR= 1.044; 95% CI: 1.037-1.059; P <0.001). A similar relationship was observed in the Chinese population. Multivariate Logistic regression model showed that for each unit increase in METS-IR, the prevalence of OSA increased by 6.7% (OR= 1.067; 95% CI: 1.035-1.103; P <0.001), and apnea-hypopnea index (AHI) increased by 0.732 (β= 0.732; 95% CI: 0.573-0.732; P <0.001). Gender subgroup analysis further showed that the association between METS-IR and OSA was particularly significant in male participants (OR= 1.111; 95% CI: 1.065-1.163; P <0.001). In the ROC analysis, the area under the curve (AUC) value of METS-IR for predicting OSA was 0.777, but it is not statistically significantly different from triglyceride glucose (TyG) (AUC = 0.749; P = 0.054), body mass index (BMI) (AUC = 0.769; P = 0.269), and triglyceride glucose-body mass index (TyG-BMI) (AUC = 0.777; P = 0.996). CONCLUSION: METS-IR is significantly associated with the risk of OSA and may serve as an effective predictive marker for identifying OSA.