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Background: Few study authors examined factors influencing health-related quality of life (HRQOL) early after left ventricular assist device (LVAD) implantation., Objective: The purpose of this study was to determine whether 5 novel self-report measures and other variables were significantly associated with overall HRQOL at 3 months after LVAD surgery., Methods: Patients were recruited between October 26, 2016, and February 29, 2020, from 12 US sites. Data were collected before LVAD implantation and at 3 months post LVAD implantation. Overall HRQOL measures included the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) overall summary score (OSS) and EuroQol 5-dimension- 3L visual analog scale. Potential factors associated with overall HRQOL included 5 novel self-report measures (Satisfaction with Treatment, Being Bothered by VAD Self-care and Limitations, VAD Team Communication, Self-efficacy regarding VAD Self-care, and Stigma), and demographic and clinical characteristics. Statistics included regression analyses., Results: Of enrollees, 242 completed self-report measures at baseline, and 142 completed measures 3 months postoperatively. Patients were 55 ± 13 years old, with 21% female, 24% non-White, 39% high school or lower educated, and 47% destination therapy. Using the KCCQ-12 OSS, higher Satisfaction with Treatment was associated with a higher KCCQ-12 OSS; Being Bothered by VAD Self-care and Limitations, high school or lower education, chest incision pain, cardiac dysrhythmias within 3 postoperative months, and peripheral edema were associated with a worse KCCQ-12 OSS (R2 = 0.524). Factors associated with a worse 3-month EuroQol 5-dimension-3L visual analog scale were female sex, adverse events within 3 months post implantation (cardiac dysrhythmias, bleeding, and venous thrombosis), and chest incision pain (R2 = 0.229). No factors were associated with a higher EuroQol 5-dimension-3L visual analog scale score at 3 months., Conclusions: Two novel measures, demographics, postimplantation adverse events, and symptoms were associated with post-LVAD KCCQ-12 OSS early after surgery., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)