Purpose: To determine the intervendor variability of Agatston scoring determined with state-of-the-art computed tomographic (CT) systems from the four major vendors in an ex vivo setup and to simulate the subsequent effects on cardiovascular risk reclassification in a large populationbased cohort. Materials and Methods: Research ethics board approval was not necessary because cadaveric hearts from individuals who donated their bodies to science were used. Agatston scores obtained with CT scanners from four different vendors were compared. Fifteen ex vivo human hearts were placed in a phantom resembling an average human adult. Hearts were scanned at equal radiation dose settings for the systems of all four vendors. Agatston scores were quantified semiautomatically with software used clinically. The ex vivo Agatston scores were used to simulate the effects of different CT scanners on reclassification of 432 individuals aged 55 years or older from a population-based study who were at intermediate cardiovascular risk based on Framingham risk scores. The Friedman test was used to evaluate overall differences, and post hoc analyses were performed by using the Wilcoxon signed-rank test with Bonferroni correction. Results: Agatston scores differed substantially when CT scanners from different vendors were used, with median Agatston scores ranging from 332 (interquartile range, 114-1135) to 469 (interquartile range, 183-1381; P <.05). Simulation showed that these differences resulted in a change in cardiovascular risk classification in 0.5%-6.5% of individuals at intermediate risk when a CT scanner from a different vendor was used. Conclusion: Among individuals at intermediate cardiovascular risk, state-of the-art CT scanners made by different vendors produced substantially different Agatston scores, which can result in reclassification of patients to the high-or low-risk categories in up to 6.5% of cases.