Abstract Background/Objectives: The United States has experienced modest increase in HPV vaccination uptake in the last decade, but remain short of the goal of vaccinating 80% of eligible adolescents by the year 2020. One known factor (barrier) associated with vaccine uptake is cost. The Affordable Care Act (ACA) came into full effect in 2014 in the United States, with an overarching aim to increase access to preventive healthcare services, including recommended vaccines, such as the HPV vaccine. This study aimed at evaluating the association between the ACA and known HPV vaccination-enabling factors in the United States. Methods: The National Health Interview Survey was queried for individuals 18-26 years from 2011 to 2017. Changes in vaccination-enabling factors (regular physician visitation [defined as physician's visit within 12 months], and changes in health insurance status), and HPV vaccination status pre- (2011-2013) to post-ACA (2014-2017) were assessed using logistic regression models adjusted for poverty, education, marital status, comorbidities, sex, and geography. We defined HPV vaccine initiation as receiving a single vaccine dose, and completion as receiving ≥2 doses. Results: A total of 13,494 and 15,722 eligible individuals were identified pre- and post-ACA. There was a 43% increase in HPV vaccine initiation post-ACA (3.9% to 5.5%; OR 1.45, 95% CI 1.24, 1.70; p<.001), with increases primarily among non-Hispanic whites (OR 1.55, 95% CI 1.24, 1.94; p<.001) and blacks (OR 1.59, 95% CI 1.12, 2.29; p=.009). Additionally, both rate and odds of HPV vaccine completion (receiving ≥2 HPV vaccine doses) increased significantly post-ACA (12.5% to 17.8%; OR 1.62, 95% CI 1.47, 1.79; p<.001); and this increase was mostly associated with Hispanics (7.6% to 14.7%), compared with non-Hispanic whites (ORinteraction = 1.36, 95% CI 1.05, 1.77; p=.020). Post-ACA, there was significant decrease in uninsured rates, and increases in vaccination completion odds among individuals privately insured (OR 1.36, 95% CI 1.22, 1.52; p<.001), and those under Medicaid (OR 1.81, 95% CI 1.35, 2.43; p<.001). There was also a corresponding increase in the rate and odds of regular physician visitation post-ACA (53.1% to 57.1%, OR 1.17, 95% CI 1.09, 1.25; p<.001). Conclusions: The ACA is associated with increased HPV vaccination uptake, with significantly greater increases in HPV vaccination completion among ethnic minorities. These gains might be driven by an increase in vaccination-enabling factors such as decreased uninsured rates and increased physician visits. Citation Format: Nosayaba Osazuwa-Peters, Justin M. Barnes, Janine Myint, Yusuf Agamawi, Eric Adjei Boakye. The Affordable Care Act and rate of human papillomavirus (HPV) vaccine uptake in the United States [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4608.