Previous observational and quasi-experimental studies in sub-Saharan Africa have suggested the effectiveness of youth-targeted HIV prevention interventions using sport as an educational tool. No studies have yet assessed the effect of similar programs in the Caribbean. A quasi-experimental trial was conducted to assess the effectiveness of a sports-based intervention in six migrant settlements in the Puerto Plata Province of the Dominican Republic. A total of 397 structured interviews were conducted with 140 adolescents prior to, immediately following, and four months following 10-hour interventions using the Grassroot Soccer curriculum. Interview responses were coded, aggregated into composite scores, and analyzed using logistic regression, adjusting for baseline differences as well as age, sex, community, and descent. At post-intervention, significant differences were observed between groups in HIV-related knowledge (adjOR = 13.02, 95% CI = 8.26, 20.52), reported attitudes (adjOR = 12.01, 95% CI = 7.61, 18.94), and reported communication (adjOR = 3.13, 95% CI = 1.91, 5.12). These differences remained significant at four-month follow-up, though declines in post-intervention knowledge were observed in the Intervention group while gains in knowledge and reported attitudes were observed in the Control group. Results suggest that this sports-based intervention could play a valuable role in HIV prevention efforts in the Caribbean, particularly those targeting early adolescents. Further evaluation of sports-based interventions should include indicators assessing behavioral and biological outcomes, longer-term follow-up, a larger sample, randomization of study participants, and strenuous efforts to minimize loss-to-follow-up.