Whilst low density lipoprotein cholesterol (LDL-C) is widely accepted as the principal lipid fraction associated with atherosclerosis, emerging evidence suggests a causal relationship between lifelong elevations in triglyceride rich lipoprotein cholesterol (TRL-C) and cardiovascular disease (CVD) in genetic studies. To provide further evidence for the potential relevance of TRL-C and atherosclerosis, we have evaluated the relationship between TRL-C and coronary artery calcium score (CAC). We included 3,845 (49.9±8.4 years, 54% women) subjects who had no prior history of CVD, were not using lipid-lowering medications and underwent CAC evaluation. We assessed the relationship between increasing fasting TRL-C and the graded increase in CAC and to what extent TRL-C were independently associated with CAC over and above LDL-C using logistic regression models. Overall 973 (25%) of the participants had a CAC >0, and 308 (8%) had a CAC > 100. The median TRL-C level was 22 (IQR: 16 - 32) mg/dL. Individuals with CAC> 0 had higher TRL-C levels than those with CAC=0 (p<0.001). Similarly, individuals with CAC> 0 had higher levels of LDL-C, non-high density lipoprotein cholesterol (non-HDL-C), and lower HDL-C (all p<0.001). After multivariate adjustment, log transformed TRL-C remained associated with the presence and severity of CAC (all p<0.05). When TRL-C was added to models which contained demographic factors and conventional lipids it significantly improved the model to predict the presence of CAC >0 (p=0.01). In conclusion, in a large cohort of asymptomatic individuals, TRL-C was associated with subclinical atherosclerosis supporting a potentially causal role in CVD.