(450 words limit, now 433)Background: Mobile health (mHealth) technology provides innovative ways to deliver weight loss interventions. Understanding how engagement in mHealth interventions relates to weight change may help develop more effective intervention strategies. Objectives: To examine 1) patterns of participant engagement overall and in key intervention features within the interventions of the Cell Phone Intervention For You (CITY) clinical trial, 2) associations of engagement with weight change, and 3) characteristics of participants that are related to engagement. Methods: The CITY trial tested two 24-month behavioral weight loss interventions. One was delivered with a smartphone application (app) (Cell Phone; CP) that contained 24 features (weighing, tracking of diets, etc.) and included regular prompting by the app in pre-determined frequency and forms. The other intervention was delivered by a coach via monthly phone calls (Personal Coaching; PC) supplemented with limited app features (18 total) and without any prompting by the app. Engagement was assessed by calculating the percentage of days each app feature was used and the frequency of usage. Engagement was also examined across four weight change categories: gained (≥2%), stable (±2%), mild loss (≥2% to <5%), and greater loss (≥5%). Results: Data from 122 CP and 120 PC participants were analyzed. Usage of the app features was highest during month 1 for both groups; thereafter, usage dropped substantially and continuously until the end of the study. During the first six months, mean percentage of days any app feature was used was higher for the CP (74.2%, standard deviation [SD], 20.1) than for the PC group (48.9%, SD, 22.4). The CP group used the app features an average of 5.3 times/day [SD, 3.1], while the PC used them 1.7 times/day [SD, 1.2]. Similarly, when the self-weighing feature was examined alone, CP self-weighed more than PC (57.1% days [SD, 23.7] vs. 32.9% [23.3]). Further, percentage of days any app feature was used, number of app usages/day and percentage of days self-weighed all showed significant differences across the four weight categories for both CP and PC. Pearson correlation coefficients showed a negative linear association between weight change and percentage of days any app feature was used (CP: r=-0.213; PC: r=-0.319), number of app usages/day (CP:r=-0.264; PC:r=-0.308), and percentage of days self-weighed (CP:r=-0.297; PC:r=-0.354). Conclusion: Engagement in CITY intervention was associated with weight loss during the first six months. Nevertheless, engagement dropped substantially early on for most intervention features. Prompting may be helpful initially. More flexible and less-intrusive prompting strategies may be needed during different stages of an intervention to increase or sustain engagement. Future studies should explore the motivations for engagement and non-engagement in order to design effective intervention. Trial Registration: NCT01092364