BACKGROUND/OBJECTIVES: Hispanic immigrants (HIs) in the U.S.A. are disproportionately affected by cervical cancer compared to other groups, at least partly due to low HPV vaccination rates. The aim of this study was to investigate strategies to improve HPV vaccine attitudes and intent of HIs in the U.S.A. by developing and testing the effectiveness of video-based interventions. METHODS: This study employed a two-phase mixed-methods approach. In the first phase, focus groups with new and established HIs explored perspectives, concerns about HPV vaccination, types of information to include in a video intervention, and how an effective intervention should be designed. Findings from the focus groups guided the creation of seven short educational videos, including a summary video and a testimonial-based video, addressing key questions about HPV and its vaccine. The second phase, which involved a nationwide survey of 1500 Spanish-speaking HIs, revealed a significant change in overall HPV vaccine attitude generally, and a significant increase in both HPV vaccine intent and attitudes among parents of unvaccinated children. RESULTS: Regression analysis revealed general vaccine attitudes (β = 0.620, < 0.001), English proficiency (β = 0.066, = 0.01), and gender (β = -0.072, = 0.002), as significant predictors of attitudinal changes. Notably, females exhibited less favorable post-intervention attitudes compared to males. Additionally, perceived care from video creators was a strong predictor of normalized gains in vaccine attitudes (β = 0.270, < 0.001). Video content effectiveness varied; the video addressing vaccine side effects demonstrated the highest impact on attitude improvement. Testimonials and the summary video were also effective in fostering positive changes in attitudes. Despite differences in trust levels between new and established immigrants, both groups valued culturally tailored, Spanish-language information from credible sources. CONCLUSION: Addressing language and cultural barriers can improve trust in healthcare interventions among Hispanic immigrants in the U.S.A. Public health initiatives should consider these factors to more effectively reduce HPV vaccine hesitancy in this population.