Over 70% of Veterans who receive health care at the VA are overweight or obese, and obesity rates of Veterans receiving care at the VA are higher compared to non-Veterans and Veterans who do not use the VA. Obesity contributes to loss of mobility which is a significant determinant of morbidity and loss of independence. Obesity also is associated with elevated cardiometabolic risk factors, including lipid profile, insulin resistance, hypertension, and inflammation. Though weight loss of as little as 3% improves physical functioning and reduces type 2 diabetes and cardiovascular risk factors, most subjects are unsuccessful at long-term weight maintenance, regaining almost half the weight lost within the following two years and return to baseline weight within the next 3-5 years. This clinical trial takes on the challenge of maintaining weight reduction by altering energy balance and possibly skeletal muscle substrate oxidation to mitigate weight regain in overweight and obese older Veterans with mobility limitations. The objective of this award proposal is to test in a randomized clinical trial the effectiveness of an intensive weight management program with and without intermittent fasting (IF) to combat weight regain and the obesity crisis in our Veterans. IF refers to short periods of intense energy restriction. We propose to enroll a total of 200 overweight and obese Veterans with mobility impairments into a 12 weeks weight loss program that incorporates a low calorie Heart Healthy (HH) diet and exercise at the Baltimore and Atlanta VAMCs. Following weight loss (WL), Veterans will be randomized to weight maintenance (WM: continuation of HH and exercise guidelines) program or weight maintenance with intermittent fasting (WM+IF) for 24 weeks. Our central hypothesis is that IF will provide the stimulus for prevention of weight regain at 36 weeks and will improve cardiometabolic and functional health factors. Further, we hypothesize that the ability to appropriately modify fuel utilization through skeletal muscle fatty acid oxidation enzymes is an important factor in weight maintenance and weight regain. This CSR&D Clinical Trial Merit Award introduces an innovative practice of IF to prevent weight relapse after clinically significant weight reduction and could provide evidence-based recommendations to promote this type of intervention in the Veteran population.