Influenza and other acute respiratory infections (ARIs) contribute significantly to human morbidity and mortality globally. Animal experiments and human challenge studies have not provided an adequate explanation about the relative importance of social, behavioral and physical environment in the transmission of ARIs and are limited due to uncertainty about the generalizability of their findings to a natural infection. Also, household transmission studies seldom characterize all potential transmission covariates e.g. environmental conditions, leaving a gap in the knowledge of transmission mechanisms. Here, we describe the design and preliminary results of an extensive college dormitory ARI transmission study that has the potential to characterize several important ARI transmission covariates; we critically appraise the design and show how the findings from such design can be applied to answer most of the vital questions that exist about the transmission of ARIs.