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Background: Aspirin-exacerbated respiratory disease (AERD) is optimally managed by endoscopic sinus surgery (ESS) followed by aspirin therapy after desensitization (ATAD). Most AERD quality of life (QOL) studies use the 22-item Sinonasal Outcomes Test (SNOT-22), which focuses predominantly on sinonasal outcomes. Objective: This study seeks to assess QOL outcomes in AERD patients after ESS and ATAD via the 12-item Short Form Survey (SF-12), a well-validated QOL measure for general health status of chronic conditions. Methods: Retrospective review of 112 AERD patients who underwent ESS followed by ATAD at our institution between 2016 and 2019. SF-12 was collected preoperatively, postoperatively/pre-AD, and serially post-AD (1–3, 4–6, 7–12, and >12 months). Optum® PRO CoRE software was used to compare data to national norms. ANOVA was performed comparing physical component summary (PCS), mental component summary (MCS) and eight health domains (physical functioning, role physical, general health, bodily pain, vitality, social functioning, role emotional, and mental health). Results: AERD patients showed improvement in PCS scores across all timepoints after ESS and ATAD (p = 0.004). When stratified by gender, women demonstrated an improvement in PCS scores (p = 0.004). Within the domains, there were significant improvements in social functioning (SF), role physical (RP), and bodily pain (BP) at all timepoints (SF: p = 0.006; RP: p = 0.005; BP: p < 0.001). Conclusions: AERD patients undergoing ESS and ATAD show improvement in physical QOL and 3 of the 8 health domains as measured by the SF-12. Future studies can use the SF-12 to study the impact of AERD treatment versus other chronic diseases and health demographics. [ABSTRACT FROM AUTHOR]