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Objective: To evaluate the extent to which postoperative complications impact patient health-related quality of life (HRQoL) and survival after pancreatic surgery. Background: Pancreatectomy is frequently associated with severe postoperative morbidity, which can affect patient recovery. Few and conflicting data are available regarding the effect of post-pancreatectomy complications on patient-reported HRQoL. Methods: This is an observational cohort study including consecutive patients enrolled in a prospective clinical trial (NCT04431076) who underwent elective pancreatectomy (2020--2022). Before surgery and on postoperative days 15, 30, 90, and 180, patients completed the PROMIS-29 profile andDuke Activity Status Index questionnaires to assess their HRQoL and functional capacity. Mean differences in HRQoL scores were obtained using multivariable linear regression adjusting for preoperative scores and confounders. Results: Of 528 patients, 370 (70%) experienced morbidity within 90 days, and 154 (29%) had severe complications (Clavien-Dindo grade >2). Delayed gastric emptying had the greatest impact on HRQoL, showing decreased mental health up to POD90 and physical health up to POD180 compared with uncomplicated patients. An inverse relationship between complication severity grade and HRQoL was evident for most domains, with Clavien- Dindo grade 3b to 4 patients showing worse HRQoL and functional capacity scores up to 6 months after surgery. In 235 pancreatic cancer patients, grade 3b and 4 complications were associated with reduced disease-specific survival (median 25 vs 41 mo, P<0.001). Conclusions: In patients undergoing pancreatic resection, postoperative complications significantly impact all domains of patient quality of life with a dose--effect relationship between complication severity and impairment of HRQoL and functional capacity. [ABSTRACT FROM AUTHOR]