BACKGROUND: Sleep disruption is linked with chronic disease, and aircraft noise can disrupt sleep. However, there are few investigations of aircraft noise and sleep in large cohorts. OBJECTIVES: We examined associations between aircraft noise and self-reported sleep duration and quality in the Nurses Health Study, a large prospective cohort. METHODS: Aircraft nighttime equivalent sound levels (Lnight) and day-night average sound levels (DNL) were modeled around 90 U.S. airports from 1995 to 2015 in 5-y intervals using the Aviation Environmental Design Tool and linked to geocoded participant residential addresses. Lnight exposure was dichotomized at the lowest modeled level of 45 A-weighted decibels [dB(A)] and at multiple cut points for DNL. Multiple categories of both metrics were compared with <45 dB(A). Self-reported short sleep duration (<7 h/24-h day) was ascertained in 2000, 2002, 2008, 2012, and 2014, and poor sleep quality (frequent trouble falling/staying asleep) was ascertained in 2000. We analyzed repeated sleep duration measures using generalized estimating equations and sleep quality by conditional logistic regression. We adjusted for participant-level demographics, behaviors, comorbidities, and environmental exposures (greenness and light at night) and examined effect modification. RESULTS: In 35,226 female nurses averaging 66.1 years of age at baseline, prevalence of short sleep duration and poor sleep quality were 29.6% and 13.1%, respectively. In multivariable models, exposure to Lnight ≥45 dB(A) was associated with 23% [95% confidence interval (CI): 7%, 40%] greater odds of short sleep duration but was not associated with poor sleep quality (9% lower odds; 95% CI: -30%, 19%). Increasing categories of Lnight and DNL ≥45 dB(A) suggested an exposure-response relationship for short sleep duration. We observed higher magnitude associations among participants living in the West, near major cargo airports, and near water-adjacent airports and among those reporting no hearing loss. DISCUSSION: Aircraft noise was associated with short sleep duration in female nurses, modified by individual and airport characteristics. https://doi.org/10.1289/EHP10959.