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BackgroundDigital interventions have been identified as a possible tool for reducing the harm caused by illicit drug use among students attending higher education (ie, college students). However, the success of interventions in this area has been hampered by a lack of user involvement and behavior change theory in their design. The My Understanding of Substance use Experiences (MyUSE) project combines a rigorous user-centered design (UCD) methodology and a robust behavioral change framework to develop a digitally delivered harm reduction intervention for illicit drug use among students in higher education. ObjectiveThis project aims to design and develop a digital intervention that targets drug use–related harm among students in higher education. MethodsThe MyUSE project will take place over 3 phases. The first phase was exploratory in nature, involving 3 systematic reviews, a large survey, and student workshops to gather a comprehensive evidence base to guide the project. The second phase is the development stage of the project, involving the use of the Behavior Change Wheel theoretical framework to determine the behavior change techniques of the intervention and the use of the UCD methodology to guide the development of the digital intervention. The third phase is the evaluation stage, whereby the intervention will undergo a 5-stage evaluation process to comprehensively evaluate its impacts. ResultsThe exploratory phase 1 of the MyUSE project was completed in December 2018. Phase 2 is currently underway, and phase 3 is due to begin in September 2020. ConclusionsHigher education institutions (HEIs) are ideally placed to intervene and support students in the area of illicit drug use but are constrained by limited resources. Current digital interventions in this area are sparse and have several weaknesses. The MyUSE project combines a UCD approach with a robust behavior change framework to develop a digitally delivered intervention that is economically viable, effective in changing behavior, usable and acceptable to students, and able to sustain long-term implementation in HEIs. International Registered Report Identifier (IRRID)DERR1-10.2196/17829