The purpose of the study was to perform phantom studies to assess the impact of computed tomography (CT) system variability on quantitative measurements of contrast enhancement. A phantom containing tubes of contrast material at dilutions of 120, 1:35, 1:50, 1:100 and 1:200 arranged in air or water was imaged using 11 CT systems at 9 institutions. All systems had undergone routine calibration against air and water in accordance with the manufacturers' recommendations. For a given tube voltage, the relationship between the iodine concentration and CT attenuation value on a single system varied by 17 to 24% over 46-48 weeks. The coefficients of variance for iodine calibration factors across different CT systems were 8.9% in air and 5.1% in water. Calibration of individual CT systems for iodine response is required to allow comparison of quantitative measurements of contrast enhancement across different institutions. Using the iodine calibration factor to express contrast enhancement as iodine concentration would facilitate the universal application of diagnostic enhancement thresholds, especially if the necessary calculations were performed by software installed on the CT console.