High coronary calcium scores are known to be associated with elevated all-cause mortality. Moreover, low response to clopidogrel influences cardiovascular outcome after coronary stent placement. We sought to evaluate whether elevated calcium scores measured by cardiac computed tomography are associated with a higher residual platelet aggregation (RPA) after treatment with clopidogrel. Thus, in 62 patients coronary calcium scoring was measured prior to stent implantation. RPA was assessed by ADP (20 micromol/L)-induced aggregometry at least 6 h after administration of a loading dose of 600 mg clopidogrel. We found a significant correlation between ASE and RPA (r2 = 0.135, p = 0.0033, slope 7.809 +/- 2.549). Patients within the first quartile of ASE had significantly lower RPA after administration of clopidogrel than other patients (p < 0.05). Establishing a threshold of 200 ASE responsiveness to clopidogrel could be predicted with a positive predictive value of 80% and a specificity of 91%. In conclusion, we could demonstrate that patients with a low coronary plaque burden are more likely to have low RPA. Coronary calcium scoring might help to identify low responders to clopidogrel prior to stent placement and aggregometry.