Previous studies indicated the effect of fat on autoimmune diseases. The present study was aimed to investigate the association between fat intake and vitiligo.This case-control study was conducted in the Skin and Leishmania Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Intakes of fatty acids were examined for their relation to risk of vitiligo among 100 cases and 110 controls. We included patients who suffered from generalized or localized vitiligo for <5 years that was approved by a dermatologist via the Vitiligo European Task Force criteria and the vitiligo area scoring index. Fat intake was assessed through individual interviews by a standardized food frequency questionnaire.Vitiligo group consumed more saturated fatty acid (SFA) and less eicosapentaenoic acid and docosahexaenoic acid than control group, while other fatty acids were not significantly different among two groups ( > 0.05). Crude analysis showed that total fat (odds ratio [OR] = 3.33, 95% confidence interval [CI]: 1.46-7.58) and SFA (OR = 2.22, 95% CI: 1.04-4.90) intakes were associated with an increased risk of vitiligo (for highest quartile vs. lowest quartile). Results demonstrated a decrease in the risk of vitiligo for those within the highest quartile of monounsaturated fatty acids intake (OR = 0.41, 95% CI: 0.18-0.92). However, this relationship disappeared after adjustment for confounders as energy, age, sex, and body mass index, except for total fat (OR = 2.84, 95% CI: 1.63-5.44). Crude and adjusted analyses for polyunsaturated fatty acids and cholesterol intake were not statistically significant.Total-fat content of the diet had more impressive role than the specific subclasses of fats on the incidence risk of vitiligo. High-fat diet escalated the vitiligo risk. Regarding the role of fats on skin autoimmune diseases especially vitiligo, future studies are crucial.