BACKGROUND: Integrating stakeholder involvement in complex health intervention design maximizes acceptability and potential effectiveness. However, there is little methodological guidance about how to integrate evidence systematically from various sources in this process. Scientific evidence derived from different approaches can be difficult to integrate and the problem is compounded when attempting to include diverse, subjective input from stakeholders. OBJECTIVE: The intent of the study was to describe and appraise a systematic, sequential approach to integrate scientific evidence, expert knowledge and experience, and stakeholder involvement in the co-design and development of a complex health intervention. The development of a Web-based lifestyle intervention for people in retirement is used as an example. METHODS: Evidence from three systematic reviews, qualitative research findings, and expert knowledge was compiled to produce evidence statements (stage 1). Face validity of these statements was assessed by key stakeholders in a co-design workshop resulting in a set of intervention principles (stage 2). These principles were assessed for face validity in a second workshop, resulting in core intervention concepts and hand-drawn prototypes (stage 3). The outputs from stages 1-3 were translated into a design brief and specification (stage 4), which guided the building of a functioning prototype, Web-based intervention (stage 5). This prototype was de-risked resulting in an optimized functioning prototype (stage 6), which was subject to iterative testing and optimization (stage 7), prior to formal pilot evaluation. RESULTS: The evidence statements (stage 1) highlighted the effectiveness of physical activity, dietary and social role interventions in retirement; the idiosyncratic nature of retirement and well-being; the value of using specific behavior change techniques including those derived from the Health Action Process Approach; and the need for signposting to local resources. The intervention principles (stage 2) included the need to facilitate self-reflection on available resources, personalization, and promotion of links between key lifestyle behaviors. The core concepts and hand-drawn prototypes (stage 3) had embedded in them the importance of time use and work exit planning, personalized goal setting, and acceptance of a Web-based intervention. The design brief detailed the features and modules required (stage 4), guiding the development of wireframes, module content and functionality, virtual mentors, and intervention branding (stage 5). Following an iterative process of intervention testing and optimization (stage 6), the final Web-based intervention prototype of LEAP (Living, Eating, Activity, and Planning in retirement) was produced (stage 7). The approach was resource intensive and required a multidisciplinary team. The design expert made an invaluable contribution throughout the process. CONCLUSIONS: Our sequential approach fills an important methodological gap in the literature, describing the stages and techniques useful in developing an evidence-based complex health intervention. The systematic and rigorous integration of scientific evidence, expert knowledge and experience, and stakeholder input has resulted in an intervention likely to be acceptable and feasible.