BackgroundAccording to the Elaboration Likelihood Model, persuasion can occur via two different routes (the central route and peripheral route), with the route utilized dependent on factors associated with motivation and ability. This study aimed to explore the moderating role of need for cognition (NFC) and perceived relevance on the processing of physical activity messages designed to persuade via either the central route or the peripheral route.MethodParticipants (N= 50) were randomized to receive messages optimized for central route processing or messages optimized for peripheral route processing. Eye-tracking devices were used to assess attention, which was the primary outcome. Message perceptions and the extent of persuasion (changes in physical activity determinants) were also assessed via self-report as secondary outcomes. Moderator effects were examined using interaction terms within mixed effects models and linear regression models.ResultsThere were no detected interactions between condition and NFC for any of the study outcomes (allps > .05). Main effects of personal relevance were observed for some self-report outcomes, with increased relevance associated with better processing outcomes. An interaction between need for cognition and personal relevance was observed for perceived behavioral control (p= 0.002); greater relevance was associated with greater perceived behavioral control for those with a higher need for cognition.ConclusionMatching physical activity messages based on NFC may not increase intervention efficacy. Relevance of materials is associated with greater change in physical activity determinants and may be more so among those with a higher NFC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12529-022-10107-4.