The purpose of this study is to investigate the effects of CT scanning and reconstruction parameters on automated segmentation and volumetric measurements of nodules in CT images. Phantom nodules of known sizes were used so that segmentation accuracy could be quantified in comparison to ground-truth volumes. Spherical nodules having 4.8, 9.5 and 16 mm diameters and 50 and 100 mg cc⁻¹ calcium contents were embedded in lung-tissue-simulating foam which was inserted in the thoracic cavity of a chest section phantom. CT scans of the phantom were acquired with a 16-slice scanner at various tube currents, pitches, fields-of-view and slice thicknesses. Scans were also taken using identical techniques either within the same day or five months apart for study of reproducibility. The phantom nodules were segmented with a three-dimensional active contour (3DAC) model that we previously developed for use on patient nodules. The percentage volume errors relative to the ground-truth volumes were estimated under the various imaging conditions. There was no statistically significant difference in volume error for repeated CT scans or scans taken with techniques where only pitch, field of view, or tube current (mA) were changed. However, the slice thickness significantly (p < 0.05) affected the volume error. Therefore, to evaluate nodule growth, consistent imaging conditions and high resolution should be used for acquisition of the serial CT scans, especially for smaller nodules. Understanding the effects of scanning and reconstruction parameters on volume measurements by 3DAC allows better interpretation of data and assessment of growth. Tracking nodule growth with computerized segmentation methods would reduce inter- and intraobserver variabilities.