This chapter discusses the lessons and aspects of study conduct of the CATIE schizophrenia trial that may be of value to researchers seeking to implement large, multi-site clinical trials and to those seeking to better understand the study design and results. The CATIE design includes multiple phases to answer questions beyond those that could be answered in the initial randomization. Three of the follow-up phases provided information, with the benefit of randomized treatment assignments, about specific clinical situations. The CATIE findings strongly suggest that, if people can enter a study on a medication to which they can be randomized, then the randomization should be stratified by incoming medication so that bias can be minimized. Based on the CATIE study and lessons learned, the chapter offers the suggestions that might be beneficial for investigators planning large scale studies.