Aircraft noise can disrupt sleep and impair recuperation. The last U.S. investigation into the effects of aircraft noise on sleep dates back more than 20 years. Since then, traffic patterns and the noise levels produced by single aircraft have changed substantially. It is therefore important to acquire current data on sleep disturbance relative to varying degrees of aircraft noise exposure in the U.S. that can be used to check and potentially update the existing noise policy. This manuscript describes the design, procedures, and analytical approaches of the FAA’s National Sleep Study. Seventy-seven U.S. airports with relevant nighttime air traffic from 39 states are included in the sampling frame. Based on simulation-based power calculations, the field study aims to recruit 400 participants from four noise strata and record an electrocardiogram (ECG), body movement, and sound pressure levels in the bedroom for five consecutive nights. The primary outcome of the study is an exposure–response function between the instantaneous, maximum A-weighted sound pressure levels (dBA) of individual aircraft measured in the bedroom and awakening probability inferred from changes in heart rate and body movement. Self-reported sleep disturbance due to aircraft noise is the secondary outcome that will be associated with long-term average noise exposure metrics such as the Day–Night Average Sound Level (DNL) and the Nighttime Equivalent Sound Level (Lnight). The effect of aircraft noise on several other physiological and self-report outcomes will also be investigated. This study will provide key insights into the effects of aircraft noise on objectively and subjectively assessed sleep disturbance.