Background and aims <p>Oxidative stress plays a crucial role in the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD). While antioxidant-rich diets may help reduce this stress and possibly reduce MASLD risk, there is little long-term evidence. This prospective study examined the link between the Composite Dietary Antioxidant Index (CDAI) and MASLD risk.</p> Methods <p>This study followed 5,988 participants (49.3% male) without MASLD at baseline from the Monitoring of Metabolic Diseases Risk Factors in Tehran (MMRT) cohort. Dietary intake was assessed using a validated 125-item food frequency questionnaire to determine the CDAI. Cases of MASLD were identified using transient elastography and at least one cardiometabolic risk factor. The association between CDAI and MASLD risk was analyzed through multivariable logistic regression.</p> Results <p>Following a five-year follow-up, 550 new cases of MASLD were identified. After adjusting for multiple confounders, individuals in the highest quartile of CDAI exhibited a 40% reduction in the risk of developing MASLD compared to those in the lowest quartile (OR: 0.60, 95% CI: 0.40–0.89; <i>p</i>-trend = 0.002). Additionally, each one-unit increment in CDAI significantly corresponded to an 8% decrease in MASLD risk. An inverse dose-response relationship was also observed between CDAI and incident MASLD, with C-reactive protein (CRP) mediating 48% of this association. Among CDAI components, increased consumption of Vitamin C and Vitamin E was independently associated with a significantly reduced risk of MASLD.</p> Conclusion <p>A higher intake of dietary antioxidants was significantly associated with a reduced risk of developing MASLD. These results indicate that encouraging antioxidant-rich dietary patterns may serve as a lifestyle modification approach for the primary prevention of MASLD.</p>