Behavioral weight loss programs help people achieve clinically meaningful weight losses (8-10% of starting body weight). Despite data showing that only half of participants achieve this goal, a “one size fits all” approach is normative. This weight loss intervention science gap calls for adaptive interventions that provide the “right treatment at the right time for the right person”. Sequential Multiple Assignment Randomized Trials (SMART), use experimental design principles to answer questions for building adaptive interventions including whether, how, or when to alter treatment intensity, type, or delivery. The BestFIT study is a SMART designed to evaluate the optimal timing for intervening with weight loss treatment non-responders and the relative efficacy of two treatments that address self-regulation challenges which impede weight loss: 1) augmenting treatment with portion-controlled meals (PCM) which decrease the need for self-regulation; and 2) switching to acceptance-based behavior treatment (ABT) which boosts capacity for self-regulation. The primary aim is to evaluate the benefit of changing treatment with PCM versus ABT. The secondary aim is to evaluate the best time to intervene with nonresponders. The symposium goals are to: 1) describe the BestFIT SMART study design and the development of the decision rules for study implementation, including re-randomization of study participants to the second stage treatments (PCM versus ABT); 2) describe the operationalization of study decision rules, recruitment methods, and early study implementation based on the first 100 study participants; and 3) discuss lessons learned and recommendations for designing SMARTs including strategies for optimizing implementation.