Abstract Disclosure: E. Mun: None. H. Lee: None. J. Choi: None. R. Lee: None. K. Kim: None. H. Kim: None. Purpose: Obesity and diabetes are rising concerns among adolescents. There are several studies regarding to the association between thyroid function and IR. However, there are limited studies focus on adolescents. Furthermore, there is a lack of studies evaluating various IR indices. We investigated the association between thyroid function and insulin resistance indices in adolescents with normal thyroid function. Methods: This cross-sectional study included 465 adolescents (aged 12-18, 255 boys, 210 girls) based on data from the Korea National Health and Nutritional Examination Survey2014-2015. Thyroid function was assessed using serum thyrotropin (TSH) and free thyroxine (fT4), while IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (GIR), TyG (triglyceride-glucose index), and TG/HDL. Multiple linear regression analyzed the relationship between thyroid function and IR, stratified by sex. Nonlinearity was assessed through a restricted cubic spline model. Results: The mean TSH (uIU/mL) and fT4 (ng/dL) were 2.70 and 1.29, respectively. Boys had higher TSH (2.86 vs. 2.52, p = 0.013) and fT4 (1.33 vs. 1.24, p < 0.001) than girls, with significant gender differences. In girls, fT4 negatively correlated with HOMA-IR and positively with GIR. No significant relationship was found between thyroid function and IR in boys. When analyzed stratified by level of obesity, the association between IR and thyroid function was clear in the overweight/obese group in both sexes. Overweight and obese groups showed relationships between fT4 and HOMA-IR (β = 0.08, p = 0.04 in boys; β = -0.12, p < 0.01 in girls) and QUICKI (β = -4.14, p = 0.03 in boys; β = 6.60, p < 0.01 in girls). TSH correlated with TyG (β = 1.01, p = 0.04 in boys; β = 1.38, p = 0.01 in girls). In girls, fT4 was also related to TG/HDL (β = -0.06, p < 0.05) and GIR (β = 0.14, p < 0.01). Nonlinear analysis found no significant relationship between thyroid function and IR. Conclusion: The relationship between thyroid function and IR was more pronounced in the overweight and obese groups. Our study suggests that the correlation between thyroid function and insulin resistance in adolescents may vary based on gender and IR indices. Presentation: 6/1/2024