The immense progress made in childhood cancer survival has been due to the systematic and efficient conduct of large multicenter therapeutic trials, using the infrastructure developed by national cooperative groups. These therapeutic trials have been successful, in part due to the high participation rates by the participating member institutions. However, participation in nontherapeutic trials in the cooperative group setting has lagged behind that of therapeutic trials for a variety of reasons, such as lack of institutional resources, leading to low priority given to such activities. The purpose of this report is to share some of the methods developed and successfully implemented by a coordinating center (City of Hope National Medical Center) to maximize institutional participation and patient enrollment and to standardize data collection and quality control, in order to ensure the successful execution of two large, extramurally funded, cooperative group nontherapeutic studies. To date, over 175 institutions have obtained regulatory approval for the protocols showcased here, accrual has been on target, and completeness and quality of the collected data have been excellent. The successful execution of these nontherapeutic studies shows the advantages of diverse study publicity techniques, detailed standardized operating procedures, and effective utilization of technological resources. Copyright © 2008 American Association for Cancer Research.