Abstract Background: U.S. Vietnamese experience higher cervical cancer incidence and have lower human papillomavirus vaccine (HPVV) uptake compared to other racial/ethnic groups. Limited research has examined multilevel determinants of HPVV uptake among this population. This study used the P3 (practice-, provider-, and patient- level) model to examine multilevel determinants of U.S. Vietnamese parents’ HPVV initiation for their children. Methods: In 2020, we conducted an online cross-sectional survey of Vietnamese parents living in the U.S. who had ≥ one child aged 9-18. Parents were recruited through U.S. Vietnamese community-based organizations, U.S. Vietnamese-focused Facebook groups and listserv, and snowball sampling. Descriptive statistics and Chi-square tests were conducted to understand facilitators of and barriers to HPVV initiation (i.e. 1+ vaccine dose). Results: The sample represented 331 Vietnamese parents in 35 U.S. states. The majority of parents were female (84.6%), had ≥ Bachelor’s degree (87.3%), and an annual household income of $50,000+ (65.6%); 98.8% were born outside of the U.S, and 60.7% had difficulties understanding English medical information. Less than half of parents initiated HPVV for their children (43.5%). HPVV initiation significantly differed by whether parents had seen materials about HPVV at their children’s clinic (62.3% vs 26.2%, p<.001). The most common facilitator of adolescent HPVV initiation was a doctor’s recommendation (80.0%) however, 55.3% reported that they had not received a doctor’s recommendation for HPVV for their children, and 59.7% of non- initiators indicated that not receiving a doctor’s recommendation was a barrier. A higher percentage of parents of female children reported HPVV initiation compared to parents of male children (52.4% vs 33.3%, p<.001). Almost all parents reported a high degree of trust in scientists who develop vaccines, CDC, and FDA (>90%) and believed that vaccines recommended for adolescents are safe (97%). Discussion: While this sample of U.S. Vietnamese parents has overall high socioeconomic status, adolescent HPVV initiation (43.5%) was still much lower than general U.S. populations (68.1% in 2018 NIS-Teen data), necessitating additional efforts to improve HPVV uptake among U.S. Vietnamese. Some findings were well-identified barriers (e.g., a lack of doctor’s recommendation, child’s sex) while others were novel (e.g., lack of access to clinic-based materials about HPVV). Findings regarding high degree of trust in vaccines and regulatory bodies can be incorporated in future interventions. Citation Format: Milkie Vu, Carla J. Berg, Cam Escoffery, Victoria N. Huynh, Robert A. Bednarczyk. A multilevel exploration of determinants of human papillomavirus vaccine initiation among U.S. Vietnamese [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-241.