Background/Aims:Preventing the development of childhood obesity requires multilevel, multicomponent, comprehensive approaches. Study designs often do not allow for systematic evaluation of the efficacy of individual intervention components before the intervention is fully tested. As such, childhood obesity prevention programs may contain a mix of effective and ineffective components. This article describes the design and rationale of a childhood obesity preventive intervention developed using the multiphase optimization strategy, an engineering-inspired framework for optimizing behavioral interventions. Using a series of randomized experiments, the objective of the study was to systematically test, select, and refine candidate components to build an optimized childhood obesity preventive intervention to be evaluated in a subsequent randomized controlled trial.Methods:A 24full factorial design was used to test the individual and combined effects of four candidate intervention components intended to reduce the risk for childhood obesity. These components were designed with a focus on (a) improving children’s healthy eating behaviors and nutrition knowledge, (b) increasing physical activity and reducing sedentary activity in the childcare setting, (c) improving children’s behavioral self-regulation, and (d) providing parental web-based education to address child target outcomes. The components were tested with approximately 1400 preschool children, ages 3–5 years in center-based childcare programs in Pennsylvania, the majority of which served predominantly Head-Start eligible households. Primary child outcomes included healthy eating knowledge, physical and sedentary activity, and behavioral self-regulation. Secondary outcomes included children’s body mass index and appetitive traits related to appetite regulation.Results:Four intervention components were developed, including three classroom curricula designed to increase preschool children’s nutrition knowledge, physical activity, and behavioral, emotional, and eating regulation. A web-based parent education component included 18 lessons designed to improve parenting practices and home environments that would bolster the effects of the classroom curricula. A plan for analyzing the specific contribution of each component to a larger intervention was developed and is described. The efficacy of the four components can be evaluated to determine the extent to which they, individually and in combination, produce detectable changes in childhood obesity risk factors. The resulting optimized intervention should later be evaluated in a randomized controlled trial, which may provide new information on promising targets for obesity prevention in young children.Conclusion:This research project highlights the ways in which an innovative approach to the design and initial evaluation of preventive interventions may increase the likelihood of long-term success. The lessons from this research project have implications for childhood obesity research as well as other preventive interventions that include multiple components, each targeting unique contributors to a multifaceted problem.