Abstract Introduction: Post-mastectomy radiotherapy (PMRT) is an important component of breast cancer treatment and has been shown to improve overall survival for women with large cancers or node positive disease. The long-term effects of radiotherapy on the outcomes of immediate breast reconstruction (IBR) and how these are perceived from the patients’ perspective, however, are largely unknown. The UK Brighter study aimed to evaluate the long-term impact of PMRT on the patient-reported outcomes of IBR to support informed decision-making. Methods: Women who underwent unilateral mastectomy and/or breast reconstruction for invasive breast cancer or ductal carcinoma in situ (DCIS) in England between 1/4/2008 and 31/3/2009 were identified from National Health Service (NHS) Hospital Episode Statistics (HES), and current contact information for the surviving cohort provided by the NHS Personal Demographic Service. Women were sent a letter inviting them to complete three validated patient-reported outcome questionnaires, the BREAST Q, EQ-5D-5L and ICECAP-A, electronically or by post at a minimum of 12 years following their index surgery. Questionnaires were scored according to developers’ instructions and scores for women who had received PMRT following IBR compared with those who underwent IBR without radiotherapy, in the cohort as a whole and by reconstruction type. Results: 11,977 women were invited to participate of whom 4,207 (35.1%) completed the questionnaires. Some 1,236 (29.4%) underwent IBR with 343 (27.8%) expander/implant (EI) reconstructions, 629 (50.9%) latissimus dorsi (LD) flaps with or without (+/-) an implant, and 264 (21.4%) abdominal flap (AF) reconstructions. Of these, 388 (31.4%) (EI n=79 (20.4%); LD+/-implant n=222 (57.2%); AF n=87 (22.4%) received PMRT. In the cohort overall, women who received PMRT following IBR reported significantly lower ‘Satisfaction with Breasts’ scores at 12 years compared with those who did not receive radiotherapy (PMRT mean 56.4. standard deviation (SD) 21.5 vs. no PMRT mean 61.3, SD 20.5), p< 0.001). However, this difference varied across procedure types. Specifically, the ‘Satisfaction with Breasts’ scores of women receiving PMRT following AF reconstruction were 10.5 points lower than those not receiving PMRT (PMRT mean 60.9, SD 20.2; no PMRT mean 71.4, SD 19.6, p< 0.001). This difference was lower in in women undergoing LD reconstruction (mean with PMRT 54.3, SD 21.1; mean without PMRT 61.6, SD 20.7; p< 0.001). There were no significant differences in women undergoing EI reconstruction (PMRT mean 57.5, SD 23.6, no PMRT mean 53.9, SD 17.7). ‘Physical Well-being’ (chest) scores were also significantly lower in women receiving PMRT following IBR in the cohort overall (PMRT mean 78.7, SD 20.1, no PMRT 83.6, SD 18.6, p< 0.001) but women undergoing AF reconstruction showed the greatest difference in scores (PMRT mean 83.2, SD 17.0 vs No PMRT mean 90.1, SD 15.0, p< 0.001). There were no significant differences in ‘Physical Well-being’ scores for women who underwent EI reconstruction with or without PMRT. ‘Psychosocial Well-being’ scores were lower in women receiving PMRT after IBR (PMRT mean 70.8, SD 22.0, No PMRT 75.4, SD 21.0), but again, differential effects were seen by procedure type with no significant differences seen in the EI group but significant differences in scores seen in women receiving PMRT after flap-based procedures. Conclusions: Women undergoing PMRT report significantly lower long-term patient-reported outcomes of flap-based reconstruction, in particular ‘Satisfaction with Breasts’ and ‘Physical Well-being’ scores. This difference was not apparent in women undergoing EI procedures. This information should be shared with patients to help them make fully informed decisions about the type and timing of their reconstructive surgery. Citation Format: Leigh Johnson, Paul White, Ranjeet Jeevan, John Browne, Carmel Gulliver-Clarke, Joe O’Donoghue, Syed Mohiuddin, William Hollingworth, Patricia Fairbrother, Mairead MacKenzie, Chris Holcombe, Shelley Potter. Impact of radiotherapy on the long-term patient-reported outcomes of immediate breast reconstruction: The UK Brighter [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-03.