Background: Negative attitudes towards #Vaccines and suboptimal #Vaccination rates among African American and Black (Black) Americans has been well documented due to a history of medical racism and human rights violations in the United States (US). However, #Digital health interventions (DHIs) have been shown to address racial disparities in several health outcomes. The Tough Talks COVID (TT-C) study was a randomized controlled trial of a DHI designed to empower Black young adults (YA) in the US South to make informed, autonomous decisions about #COVID19 #coronavirus #Vaccine uptake by addressing structural barriers and misinformation about #Vaccines. Objective: Our objective was to identify subgroups of Black YA with different #Vaccine attitudes at baseline and determine for which subgroups the TT-C DHI was most impactful. Methods: Black YA aged 18-29 years in Alabama, Georgia, and North Carolina who were un#Vaccinated or insufficiently #Vaccinated against #COVID19 #coronavirus completed three online surveys over three months (N=360). Latent profile analysis was used to identify subgroups based on general #Vaccine attitudes at baseline including hesitancy, confidence, knowledge, conspiracy beliefs, and mistrust. Logistic regression was used to examine the associations between latent profiles and #Vaccine uptake, and linear regression was used to examine changes in #Vaccines attitudes at 3 months post-randomization. Modification of the TT-C DHI’s effects were assessed by latent profiles. Results: Three latent profiles emerged: #Vaccine-receptive (n=124), #Vaccine-neutral (n=155), and #Vaccine-resistant (n=81). Political affiliation, income, social support, and recent flu #Vaccination differed significantly between the three subgroups (P