Objective: To assess the effect of reader experience on variability, evaluation time, and accuracy in the detection of coronary artery plaques with computed tomography coronary angiography (CTCA). Methods: Three independent, blinded readers with three different experience levels labelled twice 50 retrospectively ECG-gated contrast-enhanced dual-source CTCA data sets (15 female, age 67.3±10.4 years, range 4686years) indicating the presence or absence of coronary plaques. The evaluation times for the readings were recorded. Intra- and inter-observer variability expressed as k statistics and sensitivity, specificity, and negative and positive predictive values were calculated for plaque detection, with a consensus reading of the three readers taken as the standard of reference. A bootstrap method was applied in the statistical analysis to account for clustering. Results: Significant correlations were found between reader experience, and evaluation times (r=-0.59, p<0.05) and intra-observer variability (r=0.73, p<0.05). The evaluation time significantly differed among the readers (p<0.05). The observer variability for plaque detection, compared with the consensus, varied between k=0.582 and k=0.802. Variability of plaque detection was significantly smaller (p<0.05) and more accurate (p<0.05) for the most experienced reader. Conclusion: Reader experience significantly correlated with observer variability, evaluation time, and accuracy of coronary plaque detection at CTCA.