BackgroundMessage frame–tailoring based on the need for autonomy is a promising strategy to improve the effectiveness of digital health communication interventions. An example of a digital health communication intervention is Personal Advice in Stopping smoking (PAS), a web-based content-tailored smoking cessation program. PAS was effective in improving cessation success rates, but its effect sizes were small and disappeared after 6 months. Therefore, investigating whether message frame–tailoring based on the individual’s need for autonomy might improve effect rates is worthwhile. However, to our knowledge, this has not been studied previously.ObjectiveTo investigate whether adding message frame–tailoring based on the need for autonomy increases the effectiveness of content-tailored interventions, the PAS program was redesigned to incorporate message frame–tailoring also. This paper described the process of redesigning the PAS program to include message frame–tailoring, providing smokers with autonomy-supportive or controlling message frames—depending on their individual need for autonomy. Therefore, we aimed to extend framing theory, tailoring theory, and self-determination theory.MethodsExtension of the framing theory, tailoring theory, and self-determination theory by redesigning the PAS program to include message frame–tailoring was conducted in close collaboration with scientific and nonscientific smoking cessation experts (n=10), smokers (n=816), and communication science students (n=19). Various methods were used to redesign the PAS program to include message frame–tailoring with optimal usability: usability testing, think-aloud methodology, heuristic evaluations, and a web-based experiment.ResultsThe most autonomy-supportive and controlling message frames were identified, the cutoff point for the need for autonomy to distinguish between people with high and those with low need for autonomy was determined, and the usability was optimized.ConclusionsThis resulted in a redesigned digital health communication intervention that included message frame–tailoring and had optimal usability. A detailed description of the redesigning process of the PAS program is provided.Trial RegistrationNetherlands Trial Register NL6512 (NRT6700); https://www.trialregister.nl/trial/6512