BACKGROUND: Eating jetlag is an emerging concept defined as meal timing regularity between free and work days. We evaluated the association between eating jetlag and the risk of cardiovascular disease in a French cohort. METHODS: Data of 104,806 participants (79% women, mean age=42.7 years (SD 14.6)) were collected from the NutriNet-Santé prospective cohort (2009-2023). Cardiovascular disease was self-reported and validated against medical records. Eating jetlag intensity was calculated using times of first and last caloric intakes in repeated 24-hour dietary records (5.8 (SD 3.2) records on average)), as the absolute difference between weekends and weekdays, and its associations with cardiovascular disease risk were assessed through multi-adjusted Cox models. Eating jetlag direction was assessed using 3 categories: "Advance", "Maintenance", "Delay", in weekends compared to weekdays. RESULTS: During a median follow-up of 8.1 years, eating jetlag was associated, in male participants, with higher cardiovascular disease (HR = 1.14 [1.05-1.23]) and coronary heart disease (HR = 1.21 [1.11-1.33]) risks. In males, participants in the "Advance" group had higher risks of cardiovascular and coronary heart diseases (HR = 1.44 [1.08-1.93], and HR = 1.68 [1.19-2.39], respectively) compared to those in the "Maintenance" group; while those in the "Delay" group had a higher coronary heart disease risk (HR = 1.36 [1.05-1.77]). CONCLUSION: Our results suggest a role for meal timing regularity between weekends and weekdays in CVD etiology, independently of sleep duration and diet quality, specifically in males. If confirmed in other studies, meal timing regularity could be a strategy to mitigate cardiovascular disease risk. TRIAL REGISTRATION: NCT03335644.