M ost computer methods that quantify coronary artery disease from angiograms are designed to analyze frames recorded during the end-diastolic portion of the cardiac cycle. The purpose of this study was to determine if end diastole is the best portion of the cardiac cycle to sample, or if other sampling schemes produce more precise and/or reproducible estimates of coronary disease. 20 cinecoronary angiograms were selected at random from a controlled clinical trial testing the effects of plasma lipid lowering on atherosclerosis. Sampling schemes included sequential and random sampling of two to five frames within the complete cardiac cycle, systole, and diastole. Three vessel measures and percent stenosis were evaluated for each sampling scheme. From the sampling experiment, it was determined that sampling sequentially end diastole yielded the most precise estimates (i.e., exhibiting minimum variability within a cycle) of the vessel measures. With regard to reproducibility (i.e., similar values across cycles), sampling randomly within the cycle was best. Overall, the average diameter of a vessel segment was the most precise and the most reproducible of the measures. Sample size calculations are given for each of these measures under the best sampling scheme.