Background: Several studies have evaluated associations among various dietary nutrients (eg n-3 fatty acids, caffeine, magnesium) and depression in different populations. Such analyses, however, may not adequately address possible interactions among nutrients and may overlook unmeasured micronutrients. We examined the relationships among four diet patterns and depression in American Indians (AI) from the Strong Heart Family Study. Methods: Four diet patterns were extracted using factor analysis with principal component factoring method based on a sample of 3245 AI aged 14 years or older (excluding extreme calorie intakes, n=203; total var=38%). Linear Regressionmodels of the depression scale by the Center for Epidemiological Studies of Depression (CES-D) were constructed to examine the association between diet patterns and continuous CES-D measures adjusting for age, gender, BMI, waist circumference, Diabetes, education level, physical activity and Locus of Control (LOC) assessed by Multidimensional Health Locus of Control Form-B. Logistic regression models of symptoms of depression vs no depression were also run to estimate the associations of diet patterns to depression. Results: Factor 1 (in quintiles), the “less healthy” pattern, includes more fast food, snack chips, fried potatoes, prepared main dishes, sweet beverages, and animal fats. Participants who scored high on this pattern had an increase risk of depression (OR=1.09, 95%CI=1.02-1.18, p=.02). Factor 2, the “traditional AI/Southwestern” pattern consists of traditional American Indian foods common in the Southwest, as well as of meat, stew and dry beans. It is positively related to depression (OR=1.11, 95%CI=1.04-1.20, p=.002). Factor 3 resembles a healthy diet associated with fish, fruits, dark whole bread and low-fat healthier meat and dairy products. Participants who scored high on this pattern were less likely to have depression (OR=.93, 95%CI=.87-.99, p=.03). Factor 4, the “junk-food” pattern includes high amounts of coffee, tea, candy bars, sugar, syrup, animal fats, sweetened grains, doughnuts, cookies, pies, cakes, ice cream, and non-dairy creamer. Participants who scored high on this pattern were more likely to have depression (OR=1.12, 95%CI=1.05-1.20, p=.001). Depression was higher in women (OR =1.99, 95%CI=1.6-2.5, p<.001) and those with abdominal obesity (in cm; OR=1.02, p=.02) and lower in those with greater physical activity (OR=.88, p=.001), increasing age (OR=.99, p=.01), and more education (OR=.89, p<.001). Conclusion: A healthy eating pattern as well as greater physical activity and higher education were independently associated with lower depression, while depression was higher in those with central obesity. The results suggest that interventions aimed toward weight loss may also improve rates of depression in some populations.