BACKGROUND: Substance use is an alarming public health issue associated with significant morbidity and mortality. Adolescents and emerging adults are at particularly high risk because substance use typically initiates and peaks during this developmental period. Mobile health apps are a promising data collection and intervention delivery tool for substance-using youth as most teens and young adults own a mobile phone. However, engagement with data collection for most mobile health applications is low, and often, large fractions of users stop providing data after a week of use. OBJECTIVE: Substance Abuse Research Assistant (SARA) is a mobile application to increase or sustain engagement of substance data collection overtime. SARA provides a variety of engagement strategies to incentivize data collection: a virtual aquarium in the app grows with fish and aquatic resources; occasionally, funny or inspirational contents (eg, memes or text messages) are provided to generate positive emotions. We plan to assess the efficacy of SARAís engagement strategies over time by conducting a micro-randomized trial, where the engagement strategies will be sequentially manipulated. METHODS: We aim to recruit participants (aged 14-24 years), who report any binge drinking or marijuana use in the past month. Participants are instructed to use SARA for 1 month. During this period, participants are asked to complete one survey and two active tasks every day between 6 pm and midnight. Through the survey, we assess participantsí daily mood, stress levels, loneliness, and hopefulness, while through the active tasks, we measure reaction time and spatial memory. To incentivize and support the data collection, a variety of engagement strategies are used. First, predata collection strategies include the following: (1) at 4 pm, a push notification may be issued with an inspirational message from a contemporary celebrity; or (2) at 6 pm, a push notification may be issued reminding about data collection and incentives. Second, postdata collection strategies include various rewards such as points which can be used to grow a virtual aquarium with fishes and other treasures and modest monetary rewards (up to US $12; US $1 for each 3-day streak); also, participants may receive funny or inspirational content as memes or gifs or visualizations of prior data. During the study, the participants will be randomized every day to receive different engagement strategies. In the primary analysis, we will assess whether issuing 4 pm push-notifications or memes or gifs, respectively, increases self-reporting on the current or the following day. RESULTS: The microrandomized trial started on August 21, 2017 and the trial ended on February 28, 2018. Seventy-three participants were recruited. Data analysis is currently underway. CONCLUSIONS: To the best of our knowledge, SARA is the first mobile phone app that systematically manipulates engagement strategies in order to identify the best sequence of strategies that keep participants engaged in data collection. Once the optimal strategies to collect data are identified, future versions of SARA will use this data to provide just-in-time adaptive interventions to reduce substance use among youth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03255317; https://clinicaltrials.gov/show/NCT03255317 (Archived by WebCite at http://www.webcitation.org/70raGWV0e) REGISTERED REPORT IDENTIFIER: RR1-10.2196/9850