Multicenter, collaborative studies offer an effective way to meet the growing need for timely and generalizable clinical evaluations of imaging technologies. This article discusses issues of study design, statistical analysis, organization, and day-to-day group operation for collaborative prospective clinical evaluations. It draws significantly on the authors' experience with the Radiology Diagnostic Oncology Group, a cooperative group funded by the National Cancer Institute, which conducts comparative studies of the ability of diagnostic imaging modalities to enable the staging of various types of cancer including that of the prostate gland, lung, pancreas, colon, and rectum. The results from 2 1/2 years of the experience of this group hold promise for the importance of this approach to the future growth of radiologic research.