Objective: We examined the efficacy of a community-based, culturally relevant intervention to promote healthy eating and physical activity among African American (AA) women between the ages of 45-65 years, residing in rural Alabama. Methods: We conducted a group randomized controlled trial with counties as the unit of randomization that evaluated two interventions based on health priorities identified by the community: (1) promotion of healthy eating and physical activity; and (2) promotion of breast and cervical cancer screening. A total of 6 counties with 565 participants were enrolled in the study between November 2009 and October 2011. Results: The overall retention rate at 24-month follow-up was 54.7%. Higher retention rate was observed in the "healthy lifestyle" arm (63.1%) as compared to the "screening" arm (45.3%). Participants in the "healthy lifestyle" arm showed significant positive changes compared to the "screening" arm at 12-month follow-up with regard to decrease in fried food consumption and an increase in both fruit/vegetable intake and physical activity. At 24-month follow-up, these positive changes were maintained with healthy eating behaviors, but not engagement in physical activity. Conclusions: A culturally relevant intervention, developed in collaboration with the target audience, can improve (and maintain) healthy eating among AA women living in rural areas. © 2014 Elsevier Inc.