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Almost 75% of US adults are overweight or obese. Though intentional weight loss of as little as 3% improves physical functioning and reduces cardiometabolic risk, most adults are unsuccessful at long-term weight maintenance. Our hypothesis is that intermittent fasting (IF: short periods of intense energy restriction) will reduce weight regain. IF may combat obesity due to its effects on nutrient-sensing signaling pathways and circadian rhythm. The objective of this randomized clinical trial is to test the effectiveness of an intensive body weight management program with and without IF. In the Promotion of Successful Weight Management in Overweight and Obese Veterans (POWER-VET) trial (NCT04131647), 154 middle-aged and older adults (50–75 years) who are overweight and obese (BMI: 25–40 kg/m2) and seen at either a Baltimore, MD or San Antonio, TX Veterans Affairs Medical Center will be enrolled. Participants will undergo 12 weeks of weight loss (including a low-calorie heart healthy (HH) diet and exercise). Following weight loss, participants will be randomly assigned to one of two 24-week weight maintenance (WM) interventions: WM alone (continuation of HH diet and exercise) or WM + IF. The primary aim is to determine the effect of WM + IF compared to WM alone on body weight maintenance after intentional weight loss. Determining effective, translatable strategies that minimize weight regain following successful weight loss holds public health relevance. This POWER-VET trial introduces an innovative practice of IF to prevent weight regain after clinically significant weight reduction and could provide evidence-based recommendations to promote this type of intervention in middle aged and older adults. [ABSTRACT FROM AUTHOR]