How well absence of coronary artery calcium (CAC) predicts the absence of noncalcified coronary artery plaque (NCAP) has not been elucidated. We conducted a cross-sectional study of 554 outpatients to quantify NCAP prevalence as a function of CAC score. All patients underwent CAC scoring followed by 64-slice computed tomographic coronary angiography. Patients were categorized as having 0 CAC (416 patients) or low CAC (138 patients; men with CAC scores from 1 to 50 and women with scores from 1 to 10). Prevalence of detectable NCAP was 6.5% in patients with 0 CAC and 65.2% in those with low CAC. Compared with patients with 0 CAC, those with low CAC had markedly increased rates of NCAP occluding <50% of the arterial lumen (56.5% vs 6.0%, p <0.001) and > or =50% of the arterial lumen (8.7% vs 0.5%, p <0.001). In conclusion, in outpatients with a low to intermediate risk presentation and no known coronary artery disease, absence of CAC predicts low prevalence of any NCAP and very low prevalence of significantly occlusive NCAP. Low but detectable CAC scores are significantly less reliable in predicting plaque burden due to their association with high overall NCAP prevalence and nearly a 10% rate of significantly occlusive NCAP.