<p>During the COVID-19 pandemic, rapid changes in variant virulence, limited personal protective equipment availability, and diminished hospital capacity necessitated aggressive vaccine distribution. To promote COVID-19 vaccination to historically underserved populations, the National Institutes of Health funded a small group of clinical trials, including the Tough Talks for COVID-19 vaccine (TT-C) digital health intervention (DHI) randomized controlled trial (RCT). Black young adults, 18–29 years, who were unvaccinated or insufficiently vaccinated against COVID-19 were recruited via social media in Alabama, Georgia, and North Carolina and randomized to the intervention or standard of care control (<i>N</i> = 360). Self-report data and vaccine cards were collected at baseline, 1- and 3-months post-randomization. Post-intervention, 6.4% received a new COVID-19 vaccine (8.4% intervention; 4.7% control). Odds of new COVID-19 vaccination were 1.88 (CI: 0.76, 4.69, <i>p</i> = 0.174) times higher in intervention compared to control participants adjusting for state. At 3 months post-randomziation, vaccine hesitancy was lower among intervention than control participants (CI:-0.34,-0.03, <i>p</i> = 0.02), and vaccine confidence and vaccine knowledge were higher in intervention versus control participants (CI:0.00,0.32, <i>p</i> = 0.05, CI:0.21,0.79, <i>p</i> = 0.01 respectively). Under rapidly changing conditions, the TT-C DHI produced promising results on vaccine attitudes but not behaviors among Southern Black young adults. The intervention could be adapted to address vaccine uptake among other minority populations.</p><p>Trial registration: NCT05490329, registered on 03082022. </p><p><a href="https://clinicaltrials.gov/study/NCT05490329">https://clinicaltrials.gov/study/NCT05490329</a>.</p>