AbstractCluster-randomized trials (CRTs) are able to address research questions that randomized controlled trials (RCTs) of individual patients cannot answer. Of great interest for infectious disease physicians and infection control practitioners are research questions relating to the impact of interventions on infectious disease dynamics at the whole-of-population level. However, there are important conceptual differences between CRTs and RCTs relating to design, analysis, and inference. These differences can be illustrated by the adage “peas in a pod.” Does the question of interest relate to the “peas” (the individual patients) or the “pods” (the clusters)? Several examples of recent CRTs of community and intensive care unit infection prevention interventions are used to illustrate these key concepts. Examples of differences between the results of RCTs and CRTs on the same topic are given.