Research on the potential health impacts of climate change must be based on epidemiological evidence documenting risks on a global scale. Multicenter studies are well-suited for this purpose, but they present various methodological and organizational challenges. This article illustrates the experience of the international Multi-Country Multi-City (MCC) collaborative network, which is developing a comprehensive research program on the associations between weather, climate, and health. It describes how this program operates based on mutual contributions and data sharing, summarizes the main findings already published by the network, and discusses its advantages and limitations. The MCC’s contribution to research on the health effects of climate change is unique. Its collaborative approach, designed to facilitate multicenter epidemiological studies, can be replicated to address other research questions.