Background: Improving the diet of communities experiencing health inequities can be challenging given that multiple dietary components are low in quality. Mississippi Communities for Healthy Living was designed to test the comparative effectiveness of nutrition education using a single- versus multiple-message approach to improve the diet of adult residents in the Lower Mississippi Delta. Method: The single-message approach targeted discretionary calories while the multiple-message approach also targeted vegetables, fruits, whole grains, and lean protein. Delta food frequency questionnaires were used to measure participants' diet, while the Healthy Eating Index--2005 (HEI-2005) was used to generate diet quality scores. Generalized linear mixed model regression was used to test for significant time, treatment, and time × treatment interaction effects in HEI-2005 component and total score changes. Results: The majority of participants in the single- and multiple-message arms (n = 114 and 127, respectively) were female (88% and 96%, respectively), African American (90% and 98%, respectively), overweight or obese (92% and 87%, respectively), and 41 to 60 years of age (57% and 43%, respectively). Significant time effects were present for HEI-2005 total and component scores, with three exceptions--whole fruit, total grains, and saturated fat. Significant treatment effects were present for two components--total and whole fruit; scores were higher in the multiple-message approach arm as compared to the single-message approach arm across time points. No interaction effects were significant for any of the HEI-2005 scores. Conclusion: Focusing nutrition education on the discretionary calories component of the diet may be as effective as focusing on multiple components for improving diet quality.