BACKGROUND: Transgender youth demonstrate significantly higher rates of engagement in sexual risk behaviors relative to their cisgender or gender-conforming counterparts, including high rates of condomless anal intercourse and engagement in sex work. In addition, transgender youth experience increased physical or sexual abuse, victimization, substance use, mental health disorders, incarceration, and homelessness. Owing to these syndemic health disparities, transgender youth are at substantially increased risk of HIV infection. OBJECTIVE: This protocol aims to describe a randomized controlled trial (RCT), Adolescent Medicine Trials Network 160 TechStep (N=250), which assesses the differential immediate and sustained effects of each of 3 conditions (text messaging, WebApp, or information-only control) for reducing sexual risk behaviors and increasing pre-exposure prophylaxis (PrEP) uptake among high-risk, HIV-negative transgender youth and young adults (aged 15-24 years). METHODS: Participants will be recruited through web-based (targeted social media sites and apps) and offline (print ads and flyers) advertisements, peer and clinic referrals, and street- and venue-based outreach, and by contacting potential participants who have requested contact for future studies. Participants will be randomized into 1 of the 3 conditions: (1) text messaging, (2) WebApp, or (3) information-only control for 6 months. Assessments will occur at baseline and at 3, 6, and 9 months. Participants who do not show improvements in sexual risk or PrEP uptake at the 3-month assessment will be rerandomized to receive weekly electronic coaching (eCoaching) sessions in addition to their assigned text messaging or WebApp intervention, or remain in the original text messaging or WebApp intervention using a 2:1 ratio. Participants originally assigned to the information-only condition are not eligible for rerandomization. RESULTS: Funding for TechStep was awarded in June 2017. Phase 1 was approved by the Institutional Review Board (IRB) in April 2018. Recruitment began in November 2018 for phase 1, the formative phase. Initial phase 2 IRB approval came in June 2019. The data collection for phase 2, the RCT, is expected to be completed in April 2021. As of March 2020, 54 participants have been enrolled in TechStep. The final results are anticipated in May 2021. CONCLUSIONS: By providing culturally responsive, technology-based interventions, TechStep aims to improve sexual health outcomes among HIV-negative transgender youth and young adults at high risk of HIV. TechStep will evaluate the efficacy of technology-based interventions for reducing HIV sexual risk behaviors and increasing PrEP initiation, adherence, and persistence. The suite of technology-based interventions developed in TechStep, and assessed for efficacy in a 3-condition RCT, represents an important advancement in intervention science toward developing tailored and scalable interventions for transgender youth and young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT04000724; http://clinicaltrials.gov/ct2/show/NCT04000724. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18326.