© 2017 Academy of Nutrition and Dietetics Background Glycemic index (GI) and glycemic load (GL) may be implicated in acne pathogenesis. Objective This cross-sectional study examined differences between GI/GL and biological factors associated with acne among adults with and without moderate/severe acne. Secondary objectives included examining differences between food-aggravated acne beliefs and acne-specific quality of life among adults with and without moderate/severe acne. Design As part of a cross-sectional study, participants completed a 5-day food record; blood draw to measure biological factors associated with acne (ie, glucose, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and sex hormone-binding globulin concentrations); body composition assessment; and questionnaire to evaluate food-aggravated acne beliefs and acne-specific quality of life. Food records were analyzed using Nutrition Data Services for Research. Participants Sixty-four participants (no acne, n=32; moderate/severe acne, n=32) from New York City, NY, were included in this study. Statistical analysis Independent sample t tests and Mann-Whitney tests examined differences in anthropometric measurements, dietary intakes, biological factors associated with acne, insulin resistance, and acne-specific quality of life between acne groups. A χ2 test for independence assessed differences in food-aggravated acne beliefs between acne groups. Results Participants with moderate/severe acne consumed greater total carbohydrate (P=0.003), available carbohydrate (P<0.001), percent energy from carbohydrate (P<0.001), and GL (P<0.001) compared to participants without acne. Participants with moderate/severe acne had greater insulin (P=0.002) and insulin-like growth factor-1 (P=0.009) concentrations, greater insulin resistance (P=0.001), and lower sex hormone–binding globulin (P=0.015) concentrations compared to participants without acne. Although there were no differences between groups, 61% of participants reported food-influenced acne. Participants with moderate/severe acne reported a lower quality of life compared to participants without acne (P<0.001). Conclusions The results from this cross-sectional study suggest a relationship between dietary carbohydrate, including GL, and acne. Future research is necessary to determine the effect of medical nutrition therapy on biological factors associated with acne and acne severity.