Background/Objectives: Test efficacy of the social emotional learning (SEL)-based Mighty Girls program, a program culturally tailored for English-speaking Hispanic/Latino girls in seventh grade comprised of classroom sessions and a virtual reality computer game. We hypothesized that the curriculum would decrease risky sexual behaviors in a program that can be used as part of a comprehensive sex education curriculum or as a stand-alone program. Methods: A randomized group trial was conducted in which 22 low-income, predominately Hispanic schools within the Miami-Dade County Public School System were randomly assigned to intervention (consented n = 335) and control (consented n = 217) conditions. All study activities occurred after school. Primary outcome measures were resistance self-efficacy, acceptance of dating violence, sexual intentions, and sexual behavior. Assessments occurred at baseline, immediately post-intervention, 3-, 12-, and 24-months post-intervention. Changes in outcomes from baseline to 24 months were modeled using multi-level models to account for nesting of students within schools with full information maximum likelihood to account for missing data and baseline school attendance and enrollment in free and reduced lunch as covariates. Analyses are also controlled for multiple testing. Results: The program had a significant effect on reducing acceptance of dating violence at 24 months post-intervention (estimate = −0.083, p ≤ 0.05), but no effect on resistance self-efficacy, sexual intentions, or sexual behavior (p ≥ 0.58). Conclusion: Study findings demonstrate that a social emotional learning (SEL) curriculum can impact sexual behaviors such as susceptibility to dating violence. Low baseline levels for sexual intentions and behaviors as well as a high baseline of efficacy may have impacted findings for the other outcomes.