The SARS-CoV-2 pandemic focused attention on the importance of ventilation to limit acute respiratory infection (ARI) transmission. However, because few epidemiologic studies demonstrate a causal effect of building ventilation on ARI transmission investment in solutions remains at risk. We report results of a two-year ARI study of college students living in campus residence halls with a trend toward 54% lower ARI risk with higher ventilation. Our analysis suggests that the most powerful causal analysis can be derived from focusing on roommate pairs. Future studies should prioritize enrolling roommates rather than individuals and confirm transmission events through whole genome sequencing.