Abstract Purpose: To assess changes over time in health behaviors (fruit & vegetable [F&V] consumption and physical activity [PA]), physical performance (PP), and anthropometrics among chronic disease survivors (CDS) of cancer, diabetes, and heart disease participating in a home-based vegetable gardening intervention in the Deep South. Methods: A community-based partnership was developed between the O’Neal Comprehensive Cancer Center, the Alabama Cooperative Extension System, and the Mississippi State Cooperative Extension System to implement an evidence-based gardening intervention (Harvest for Health). CDS were recruited from nine counties in Alabama and six in Mississippi. All participants were provided gardening supplies and paired with a Master Gardener (MG) from the Cooperative Extension. MGs mentored participants in planning, planting, and maintaining a summer/fall garden over a 3-month period. Senior Physical Performance Battery (SPPB) and anthropometrics (weight, height, and waist circumference [WC]) were collected by trained study personnel during community-based assessments (baseline and post-intervention). Self-reported data on health behaviors (NCI's Eating at America's Table Study and modified Godin leisure-time exercise questionnaire) were collected electronically via REDCap (baseline, post-intervention, 6-month follow-up). Results: One hundred and twenty CDS enrolled in the study (66% diabetes; 34% cancer; 29% heart disease). Participants (93% African American; 81% female; Mage=65) tended to be retired/disabled (62%), have overweight or obesity (92%), and reported a family income of less than $40,000 (68%). Overall, CDS engaged in gardening for 15-45 minutes (70%), several times a week (79%). Increases were seen in PA minutes/week at post-intervention (Moderate PA +10, p=0.34; Vigorous PA +30; p=0.05) and 6-month follow-up (Moderate PA +26, p<0.01; Vigorous PA +22; p<0.01). A trend in increased F&V consumption was seen, with nearly a one serving/day increase at 6-month follow-up (3.7 vs 3.0; p=0.07). When asked to rate, on a scale of 1-10 (1=not at all to 10=very much), the influence of gardening on motivating behavior change, CDS reported that gardening motivated them to… “eat a healthier diet” (M=7.9; SD=2.1), “eat more vegetables” (M=8.2; SD=2.1), and “be more physically active” (M=7.6; SD=2.4). Improvements in anthropometrics were seen post-intervention (weight: -2 lbs.; BMI: -0.37 kg/m2; WC: -0.81 cm). Improvements in the SPPB were demonstrated in 5-of-8 measures (2-minute step test +4 steps; 30-second chair stand +0.6 rises; arm curl +1.7 curls, p<0.01; right hand grip strength +5 kg, p<0.01; right hand grip strength +5.7 kg, p<0.01). Discussions/Conclusions: The vegetable gardening intervention led to several improvements in lifestyle behaviors and outcomes among CDS in the Deep South and may offer an innovative approach to improving health among populations in need. Citation Format: Jennifer R. Bail, Meghan Tipre, Oluseun Akinyele, Bolanle Bolaji, Tara Bowman, Claudia Hardy, Wendy Demark-Wahnefried, Monica L Baskin. A home-based vegetable gardening intervention to address health behaviors and well-being among chronic disease survivors in the Deep South [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B017.