IMPORTANCE: The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials. OBJECTIVE: To determine the effect of 16:8-hour time-restricted eating on weight loss and metabolic risk markers. INTERVENTIONS: Participants were randomized such that the consistent meal timing (CMT) group was instructed to eat 3 structured meals per day, and the time-restricted eating (TRE) group was instructed to eat ad libitum from 12:00 pm until 8:00 pm and completely abstain from caloric intake from 8:00 pm until 12:00 pm the following day. DESIGN, SETTING, AND PARTICIPANTS: This 12-week randomized clinical trial including men and women aged 18 to 64 years with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 to 43 was conducted on a custom mobile study application. Participants received a Bluetooth scale. Participants lived anywhere in the United States, with a subset of 50 participants living near San Francisco, California, who underwent in-person testing. MAIN OUTCOMES AND MEASURES: The primary outcome was weight loss. Secondary outcomes from the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure. RESULTS: Overall, 116 participants (mean SD age, 46.5 10.5 years; 70 60.3% men) were included in the study. There was a significant decrease in weight in the TRE (−0.94 kg; 95% CI, −1.68 to −0.20; P = .01), but no significant change in the CMT group (−0.68 kg; 95% CI, -1.41 to 0.05, P = .07) or between groups (−0.26 kg; 95% CI, −1.30 to 0.78; P = .63). In the in-person cohort (n = 25 TRE, n = 25 CMT), there was a significant within-group decrease in weight in the TRE group (−1.70 kg; 95% CI, −2.56 to −0.83; P < .001). There was also a significant difference in appendicular lean mass index between groups (−0.16 kg/m2; 95% CI, −0.27 to −0.05; P = .005). There were no significant changes in any of the other secondary outcomes within or between groups. There were no differences in estimated energy intake between groups. CONCLUSIONS AND RELEVANCE: Time-restricted eating, in the absence of other interventions, is not more effective in weight loss than eating throughout the day. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03393195 and NCT03637855