Background: Early detection of atherosclerotic process is crucial for primary prevention of cardiovascular diseases. In this study we tested independent and added predictive value of serum molecular lipidome for subclinical atherosclerosis over traditional risk factors. Subjects and methods: We investigated significance of serum lipidome using LC-MS/MS technique in prediction of subclinical atherosclerosis assessed by carotid intima-media thickness (cIMT) in Young Finns Study cohort in 2007 (number:2009, age:30-45 years, women:55%). Statistical analysis was done with dichotomized cIMT data (cases: value ³ 90th percentile vs. controls: value <90th percentile). Differential expression analysis of lipidome data between cases and controls was performed with Student’s t-test. Lipid species that were differentially expressed between cases and controls were selected for building prediction models . Reference predictive model with major traditional risk factors and two test predictive models; one with selected lipid species and traditional risk factors (test model1) and other with selected lipid species only (test model 2) were analyzed. Predictive variables in all the models were further selected with bootstrap backward-stepwise algorithm. Model fitting and validation was done for 1000 bootstraps of the original data by: i) fitting models to training data (70% data), ii) testing the models on test data (30% data), and iii) calculate accuracy measure (ROC AUC). Results: Our results suggest that serum lipidome significantly improves prediction accuracy for subclinical atherosclerosis over traditional risk factors (reference model: AUC 0.762, 95% CI [0.698, 0.823], test model 1: AUC 0.778, 95% CI [0.715, 0.838], t-test p-value: 2.2e-16). Serum lipidome also showed independent predictive accuracy equivalent to that of traditional risk factors [test model 2: AUC 0.762, 95%CI [0.698, 0.821], t-test p-value against reference model: 0.5005]. Conclusion: This study indicates that serum lipidome may help in predicting subclinical atherosclerosis for primary prevention more effectively than traditional risk factors alone.