Abstract Purpose: This study investigated differences in swallowing-related quality of life (QoL) and weight outcomes in patients treated for oropharyngeal cancer (OPC) based on feeding tube (FT) use. Methods: A retrospective chart review of OPC patients treated with definitive radiotherapy (± chemotherapy) was performed. Swallowing QoL and weight outcomes were collected from electronic medical records for patients seen at a single regional cancer center between January 2013 and December 2015. M.D. Anderson Dysphagia Inventory (MDADI) composite scores, Performance Status Scale for Head and Neck Cancer (PSS-HN) Normalcy of Diet scores, and weight measurements were gathered at baseline and at 3, 6, and 12 months post-treatment. Patients were grouped based on FT use. Bivariate associations were evaluated using the chi-square test and change over time was analyzed by group using a linear mixed effects analysis. The proportion of patients with clinically meaningful change was also determined. Results: Of 126 eligible patients, 46 (36.5%) received a reactive gastrostomy or gastro-jejunostomy FT (FT group). Compared to baseline, MDADI composite scores were significantly lower at 3 and 6 months (p < .001) for those who did not receive a FT (NFT group), while no significant change occurred in the FT group over time. No significant change was noted in PSS-HN scores for either group. Significant decreases in weight occurred in both groups at 3 and 6 months, and at 12 months for the NFT group alone (p < .001). Clinically meaningful decreases in MDADI composite scores at 3, 6, and 12 months were observed in 53%, 43%, and 29% of FT patients and 45%, 44%, and 33% of NFT patients, respectively. Clinically meaningful decreases in weight were observed at 3, 6, and 12 months in 30%, 23%, and 13% of FT patients and for 50%, 44%, and 40% of NFT patients, respectively. There was no significant association between FT use and clinically meaningful decreases in either MDADI composite scores or weight. Conclusions: Despite selective use of enteral feeding for nutritional support in patients at risk, the impact of FT utilization on functional outcomes is not well understood. Statistically significant decreases in short-term swallowing-related QoL were noted preferentially in patients without FTs, and there was a concerning trend for NFT patients to not return to baseline weight by 12 months post-treatment. However, this study also identified that patients in both groups experienced clinically meaningful decreases in swallowing-related QoL and weight in the first year post-treatment irrespective of FT use. Based on this evidence, it is prudent to monitor weight change closely, particularly in patients who do not meet initial risk criteria for reactive FT placement. Understanding the potential for clinically meaningful change in swallowing QOL and weight will contribute to improved patient monitoring and intervention, and may ultimately lead to better outcomes for those with OPC. Citation Format: Nedeljko Jovanovic, Colleen Dreyer, Sarah Hawkins, Kendra Thouless, David Palma, Philip C. Doyle, Julie A. Theurer. Impact of feeding tube use on swallowing-related quality of life and weight in oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A36.