PURPOSE: Computed tomography (CT) might be a good diagnostic test to accurately quantify calcium in vascular beds but there are multiple factors influencing the quantification. The aim of this study was to investigate the influence of different computed tomography protocol settings in the quantification of calcium in the lower extremities using modified Agatston and volume scores. METHODS: Fresh-frozen human legs were scanned at different tube current protocols and reconstructed at different slice thickness. Two different iterative reconstruction protocols for conventional CT images were compared. Calcium was manually scored using modified Agatston and volume scores. Outcomes were statistically analyzed using Wilcoxon signed-rank tests and mean absolute and relative differences were plotted in Bland-Altman plots. RESULTS: Of the 20 legs, 16 had CT detectable calcifications. Differences between thick and thin slice reconstruction protocols were 129 Agatston units and 125% for Agatston and 78.4 mm3 and 57.8% for volume (all p ≤ 0.001). No significant differences were found between low and high tube current protocols. Differences between iDose4 and IMR reconstruction protocols for modified Agatston were 34.2 Agatston units and 17.7% and the volume score 33.5 mm3 and 21.2% (all p ≤ 0.001). CONCLUSIONS: Slice thickness reconstruction and reconstruction method protocols influenced the modified Agatston and volume scores in leg arteries, but tube current and different observers did not have an effect. This data emphasizes the need for standardized quantification of leg artery calcifications. Possible implications are in the development of a more universal quantification method, independent of the type of scan and vasculature