The prevalence of obesity is significantly higher among American Indians (AIs) and is associated with increased rates of diabetes, hypertension, and cardiovascular disease. We implemented a 14-mo intervention trial (Navajo Healthy Stores) on the Navajo Nation that sought to increase availability of healthier foods in local food stores and to promote these foods at the point of purchase and through community media. We divided the Navajo Nation into 10 store regions, half of which were randomized to intervention and half to comparison. We evaluated the program by using a pre-post sample of systematically sampled adult Navajo consumers (baseline, n = 276; postintervention, n = 145). Intervention impact was examined by analyzing pre-post differences by intervention group and by intervention exposure level. When intervention and comparison groups were compared, only body mass index (BMI) showed a trend toward impact of the intervention (P = 0.06). However, greater exposure to the intervention was associated with significantly reduced BMI (P ≤ 0.05) and improved healthy food intentions (P ≤ 0.01), healthy cooking methods (P ≤ 0.05), and healthy food getting (P ≤ 0.01). With increasing exposure, the odds of improving overweight or obese status was 5.02 (95% CI: 1.48, 16.99; P ≤ 0.01) times the odds of maintaining or worsening overweight or obese status. In summary, a food store intervention was associated with reduced overweight/obesity and improved obesity-related psychosocial and behavioral factors among those persons most exposed to the intervention on an AI reservation.