Purpose: The purpose of this study was to investigate the effect physical activity has on an attempt to quit smoking, and whether this effect varies over time and/or is mediated by other variables. Previous research has demonstrated that cravings to smoke are associated with higher odds of relapse, and that the strength of this effect increases throughout a quit attempt. A bout of physical activity has also been shown to reduce cravings to smoke. We hypothesized that physical activity would have a time-varying effect on smoking mediated by cravings to smoke. Methods: The Wisconsin Smokers Health study was a randomized, placebo-controlled trial of five smoking cessation therapies. Each day, participants measured their steps with a pedometer and used their cell phone to complete Ecological Momentary Assessments of their cravings to smoke. We analyzed data from 7-days prior to a target quit day through 7-days following quit day. Participants were grouped by their daily step count and considered “less active” if they averaged less than 10,000 steps per day. Results: We found evidence among less physically active smokers that 1,000 additional steps per day on the first 1-3 days of a quit period is associated with a lower odds of smoking relapse on those days. This effect remained significant after including covariates in subsequent models, as well as both the effects of cravings and negative affect on smoking. We were also able to replicate the previous finding in this dataset that the effect of cravings to smoke on smoking odds increases during the first week post-quit day as time from quit day increases. Despite our finding that steps per day was associated with lower relapse among inactive smokers, and that inactive smokers had higher cravings and higher relapse rates, our study did not yield evidence for our mediation hypothesis that steps per day would associate with lower cravings to smoke. Conclusion: These findings could be used to tailor smoking cessation interventions to people at high risk of relapse and failure to successfully quit. A bout of 1,000 steps is roughly a 15-minute walk. Encouraging this kind of behavior when cravings are high could lead to successful quitting for less active smokers. Future cessation research with a focus on framing physical exercise as a protective tool against smoking relapse could be valuable for creating more efficient interventions. / Public Health