White blood cell (WBC) count is associated with incident coronary heart disease (CHD). Data are sparse regarding its association in young adults with future coronary artery calcification (CAC). Our study was conducted among coronary artery risk development in young adults (CARDIA) participants (n=3,094). We examined the association between baseline (Y0) WBC counts and CHD risk factors using linear regression models. We further assessed prospective associations between Y0 WBC and inflammatory biomarkers during the follow-up, and the presence of CAC 15 and 20 years later. In total, 272 and 566 subjects had CAC scores>0 at year (Y) 15 and Y20, respectively. Baseline total WBC counts were cross-sectionally associated with SBP, BMI, and smoking, or HDL-cholesterol (p≤0.01) at Y0, and prospectively associated with C-reactive protein at Y7, Y15, and Y20, and fibrinogen at Y5 and Y20 (p<0.01). After adjustment for potential confounding factors, baseline neutrophil count was borderline associated with CAC presence 15 years later (OR=1.18 per unit, 95% CI 1.00-1.44) and total WBC (OR=1.07, 95% CI 0.96-1.19) or eosinophil (OR=1.12, 95%CI 1.00-1.25) was borderline associated with CAC presence at Y20. Baseline total WBC counts in young adults was associated prospectively with CAC presence 20 years later after adjusting for age, sex, and race. Results are attenuated when other risk factors are accounted for. Our results suggest the possible early involvement of WBC, particularly eosinophils, in the early stages of atherosclerosis.