Obese youth with prediabetes are at increased risk for premature morbidity and mortality through multiple mechanisms, including increased systemic inflammation. GlycA is a novel measure of systemic inflammation that predicts type II diabetes, cardiovascular events, and all-cause mortality in adults. The purpose of the present study was to examine changes in GlycA after lifestyle intervention among obese, prediabetic Latino youth. Obese, prediabetic Latino youth (n=27; 15.5±1.1years, 13 males/14 females) completed a 12-week lifestyle intervention that included weekly nutrition education and 3 d/wk of moderate to vigorous physical activity. Prediabetes was characterized by an expanded definition of impaired glucose tolerance, using 2-hour glucose ≥120mg/dL after an oral glucose tolerance test. GlycA was assessed at baseline and 12weeks using nuclear magnetic resonance spectroscopy. After the lifestyle intervention, GlycA was significantly reduced (445.3±51.3μmol/L to 419.0±50.0μmol/L, P=.01) (mean±standard deviation). Additional improvements were observed in multiple cardiovascular risk factors, including body mass index (BMI; 34.8±5.0kg/m2 to 34.0±5.1kg/m2, P<.001), total cholesterol (154.1±30.3mg/dL to 143.3±29.1mg/dL, P=.003), and 2-hour glucose (141.0±13.2mg/dL to 115.9±31.4mg/dL, P<.001). Decreases in GlycA were associated with decreases in 2-hour glucose (r=0.49, P=.008) and BMI (r=0.41, P=.03). These data are consistent with the hypothesis that lifestyle intervention might improve GlycA levels in obese, prediabetic adolescent Latinos, but randomized trial evidence is needed. Healthy lifestyle modifications among high-risk youth may decrease future risk of cardiometabolic disease through reducing systemic inflammation, in addition to improving traditional cardiovascular risk factors.