Abstract Background: Despite having guidelines recommending vaccination against the human papillomavirus (HPV) and widespread coverage for the vaccine, HPV vaccination rates among U.S. Hispanic and island Puerto Rican (PR) girls are low. In 2012, only 16% of PR girls aged 11–18 and 42% of U.S. Hispanic girls aged 13-17 were vaccinated with all three HPV vaccine doses; far fewer than the Healthy People 2020 goal of 80%. Parents are crucial to the success of HPV vaccine uptake efforts. Few studies focusing on parents have examined possible differences in HPV knowledge and vaccine acceptability within ethnic groups. The purpose of the study is to assess potential differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanic and island PR women. Methods: We utilized data from the Health Information National Trends Survey (HINTS) 2007 and HINTS Puerto Rico 2009. For the current study, we restricted our analyses to female respondents in both surveys for a total sample of 792 women (n = 375; U.S. Hispanic HINTS 2007 and n = 417; Puerto Rican HINTS-PR 2009). Using the Wald chi-square test, we assessed if there were significant differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanics and island PR women. Results: Island PR women had significantly higher HPV vaccine awareness (66.9% vs. 61.0%; Wald X2 F(1, 97) = 16.03, p < .001) and were more accepting of the HPV vaccine for a real or hypothetical daughter (74.8% vs. 56.1%; Wald X2 F(2, 96) = 7.18, p < .001) compared to U.S. Hispanic women. Both groups were highly knowledgeable that HPV causes cancer (89.2% in both samples) and HPV is a sexually transmitted infection (78.1% [U.S. Hispanics] and 84.7% [PR]). Less than 10% of both groups recognized that HPV can go away on its own without treatment. Conclusions: Our study found that island PR women were more aware of and accepting of the HPV vaccine when compared to U.S. Hispanic women. Future research should further explore these in-group differences to determine what in the PR socio-cultural context or environment may have led to higher HPV vaccine awareness and acceptability. Findings may also assist in developing culturally appropriate health education programs and media to promote HPV vaccination among both groups. Citation Format: Daisy Y. Morales-Campos, Robin C. Vanderpool. Examining differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanic and island Puerto Rican women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B88.