Introduction: Early metabolic imbalance (EMI) is insidiously prevalent in the U.S., especially among teens and young adults. It includes markers of insulin resistance, inflammation and oxidative stress, but does not meet the criteria for metabolic syndrome. Individuals with EMI have compensatory hyperinsulinemia, an independent risk factor for CVD. Yet, fasting insulin is an underutilized prognostic marker, partly due to a lack of calibrated cut points for this population. Hypothesis: The prognostic value of insulin for CVD risk is associated with an optimum cut point, which can be calibrated using a time-dependent receiver operator characteristic (timeROC) analysis of CARDIA: Coronary Artery Risk Development in Young Adults. Methods: The parent CARDIA study began in 1985, enrolling 5,114 participants ages 18-30 at baseline, with 35-year follow-up. In our retrospective cohort analysis, the exclusion criteria were hyperglycemia, hypertriglyceridemia, low HDL, pregnancy, diabetes, CVD, or fasting < 8 hours, all at baseline; n=3,292. The primary outcome was time to incident CVD (or censor), defined as fatal/nonfatal MI, coronary revascularization, acute coronary syndrome, CHF, stroke, TIA, carotid or peripheral artery disease. Survival data were analyzed using the ‘timeROC’ package in R v.4.2.1, with/without adjustment for the 2019 ACC/AHA risk factors for CVD. For validation, a conventional ROC (logROC) analysis was performed, with incident CVD as the outcome. For timeROC and logROC, the cut point optimum was determined using minimum distance to the [0, 1] coordinate; predictive accuracy was summarized by area under the curve (AUC). The prognostic value of insulin at its optimum was determined using Cox regression for insulin alone and with risk factors, using Stata v.17.0. Cox results are summarized with hazard ratio (HR) and Harrell’s c-statistic (c). Results: The cut point optimum for baseline fasting insulin was 9.1 mIU/L (60.5 percentile), with AUC 0.583 (95% CI: 53.6, 62.9), sensitivity 54.8% and specificity 61.7%. The results were unchanged with/without covariate adjustment in timeROC, and with logROC. Using the optimum, the unadjusted Cox HR for high vs. low insulin was 1.9 (95% CI 1.4, 2.6, p<0.0001); c=0.580. Cox model 2 included a variable with both high insulin and high waist circumference (WC); HR for both vs. neither condition was 2.6 (95% CI 1.8, 3.8, p<0.0001); c=0.606. Cox model 3 added ACC/AHA risk factors to model 2: HR 2.2 (95% CI 1.5, 3.4, p<0.0001) for high insulin and WC vs. neither; c=0.716. Conclusion: For young adults in CARDIA without metabolic syndrome or prediabetes, the cut point optimum for fasting insulin is near the top tertile. Insulin has a high prognostic value for CVD, especially when combined with WC. Though useful, insulin suffers from modest sensitivity. Better markers of EMI are needed for assessing hidden CVD risk in apparently healthy young adults.