Multicenter studies involving randomized clinical trials (RCTs) may have different structures. We discuss four general types. The first two, an "ideal" multicenter RCT and decentralized multicenter collaborative RCTs, we feel are, in different circumstances, highly recommended approaches. The other two, the multicenter RCT that ignores site differences and centralized multicenter collaborative RCTs, we argue, are not only not cost-effective but may also produce misleading results, thus impeding scientific progress and possibly putting patients at unnecessary risk.