INTRODUCTION: Smoking, obesity, and insufficient physical activity are modifiable health risk behaviors. Self-regulation is one fundamental behavior change mechanism often incorporated within digital therapeutics as it varies momentarily across time and contexts and may play a causal role in improving these health behaviors. However, the role of momentary self-regulation in achieving behavior change has been infrequently examined. Using a novel momentary self-regulation scale, this study examined how targeting self-regulation through a digital therapeutic impacts adherence to the therapeutic and two different health risk behavioral outcomes. METHODS: This prospective interventional study included momentary data for 28 days from 50 participants with obesity and binge eating disorder and 50 participants who smoked regularly. An evidence-based digital therapeutic, called Laddr™, provided self-regulation behavior change tools. Participants reported on their momentary self-regulation via ecological momentary assessments and health risk behaviors were measured as steps taken from a physical activity tracker and breathalyzed carbon monoxide. Medical regimen adherence was assessed as daily Laddr usage. Bayesian dynamic mediation models were used to examine moment-to-moment mediation effects between momentary self-regulation subscales, medical regimen adherence, and behavioral outcomes. RESULTS: In the binge eating disorder sample, the perseverance [  = 0.17, 95% CI = (0.06, 0.45)] and emotion regulation [  = 0.12, 95% CI = (0.03, 0.27)] targets of momentary self-regulation positively predicted Laddr adherence on the following day, and higher Laddr adherence was subsequently a positive predictor of steps taken the same day for both perseverance [  = 0.335, 95% CI = (0.030, 0.717)] and emotion regulation [  = 0.389, 95% CI = (0.080, 0.738)]. In the smoking sample, the perseverance target of momentary self-regulation positively predicted Laddr adherence on the following day [ = 0.91, 95% CI = (0.60, 1.24)]. However, higher Laddr adherence was not a predictor of CO values on the same day [  = -0.09, 95% CI = (-0.24, 0.09)]. CONCLUSIONS: This study provides evidence that a digital therapeutic targeting self-regulation can modify the relationships between momentary self-regulation, medical regimen adherence, and behavioral health outcomes. Together, this work demonstrated the ability to digitally assess the transdiagnostic mediating effect of momentary self-regulation on medical regimen adherence and pro-health behavioral outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier (NCT03774433).