Acute respiratory infections (ARIs) are the leading cause of acute morbidity and lost work time in the United States. Few studies have looked at building design and transmission of ARIs. This study explores the association of ventilation design, room occupancy numbers, and training week with ARI rates in Army Basic Combat Training barracks. This observational study captured the overall incidence of ARI in a cohort of 16,258 individuals attending basic combat training at Fort Jackson, South Carolina. ARI risk was higher among trainees living in the 60-person room barracks compared with those living in 8-person rooms, which increased rapidly for the first few weeks of training and then declined to baseline. Findings support direct contact as primary ARI transmission mode in this study population based on observed lower ARI risk in smaller room barracks and similar risk in large room barracks despite heating, ventilation, and air conditioning system variability.