Background: Travelers frequently experience Jet Lag Disorder (JLD) symptoms due to misalignment of the circadian rhythm with respect to the new time zone. In the JET8 Study, we assessed the efficacy and safety of tasimelteon (HETLIOZ®) in healthy participants using a laboratory model of JLD induced by an 8-h phase advance of the sleep-wake cycle. We hypothesized that tasimelteon treatment in participants experiencing JLD would cause increased sleep time, increased next-day alertness, and reduced next-day sleepiness. Methods: We undertook a randomized, double-blind, placebo-controlled trial in 12 US clinical research sleep centers. We screened healthy adults ages 18-73 years, who were eligible for the randomization phase of JET8 if they typically went to bed between 21:00 and 01:00, slept between 7-9 hours each night, and slept at a consistent bedtime. We used block randomization stratified by site to assign participants (1:1) to receive a single oral dose of tasimelteon (20mg) or placebo 30 min before their 8-h phase-advanced bedtime. The primary endpoint was Total Sleep Time in the first 2/3 of the night (TST2/3), which was measured by polysomnography during the 8-h sleep episode, and assessed in the intent-to-treat population. The trial is completed and registered with ClinicalTrials.gov, NCT03373201. Results: Between October 16, 2017 and January 17, 2018, we screened 607 healthy participants for JET8, of whom 320 (53%) were assigned to receive tasimelteon (n=160) or placebo (n=160). Tasimelteon treatment resulted in increased TST2/3 by 60.3 min (95%CI 44.0 to 76.7, P<0.0001) compared to placebo and had a highly significant benefit in secondary endpoints including TST of the whole night, next day alertness, next day sleepiness, and latency to persistent sleep. Conclusion: A single dose of tasimelteon improves symptoms, including sleep and next day functioning in participants, following an 8-h phase advance of the sleep-wake cycle in a laboratory model of JLD simulating eastward trans-meridian travel.