In 2015, only 42% of Puerto Rican (PR) girls aged 13-17 and 44% of U.S. Hispanic girls aged 13-17 were vaccinated with all three Human Papillomavirus (HPV) vaccine doses; These percentages were far lower than the Healthy People 2020 goal of 80% of girls aged 13-15 the Healthy People 2020 goal of 80%. The purpose of this study was to examine potential differences in HPV awareness and knowledge and HPV vaccine awareness and acceptability between a population-based sample of U.S. Hispanic and island Puerto Rican women.