>To our knowledge, this is the first study to examine the relationship between dietary creatine intake and risk of depression in a nationally representative U.S. sample. We found that MDD prevalence among U.S. adults follows a step-wise decrease corresponding to an incremental increase in dietary creatine consumption. Depression prevalence was 42% higher among adults in the lowest quartile (0–0.26 g) compared to adults in the highest quartile (0.70–3.16 g) of creatine consumption. In comparison, depression prevalence among persons with low creatine intake mirrors what has been estimated among persons with chronic medical conditions such as Type 2 Diabetes Mellitus50. After controlling for demographic and lifestyle variables, the risk of screening positive for depression was 31% lower among adults in the highest, compared to the lowest, quartile of creatine consumption.