Introduction: Patient reported outcomes establish the patient’s own perception about his/her health and enable the development of policies designed to improve health/disease processes. These are particularly helpful in the case of diseases with a significant impact on the patient’s quality of life. Objective: To compare the quality of life scores assessed using the EQ-5D-5L questionnaire in patients undergoing cephalic duodenopancreatectomy (Whipple procedure) and laparoscopic cholecystectomies in the same hospital. Methodology: Retrospective cohort trial between July 2018 and February 2020. Patients programmed for cephalic duodenopancreatectomy were included, regardless of the type of pathology, and over 18 years old. Patients with carcinomatosis or vascular infiltration were excluded. The EQ-5D-5L was administered following Whipple surgery and compared against a control group (laparoscopic cholecystectomy). The demographic characteristics, the diagnosis, hospital stay and 60-day mortality were assessed. Results: A total of 68 patients were included. The most frequent diagnosis was pancreatic cancer (30 %) in the Whipple group and lithiasis (100 %) in the control group. In the five dimensions assessed, there were no differences in terms of mobility (OR: 0.41, 95 % CI [0.30-0.57], p = 0.103) and in terms of personal care (OR: 0.42, 95 % CI [0.32-0.58], p = 0.254). There was a difference in daily life activities (OR: 0.38, 95 % CI [0.27-0.54], p = 0.017), pain/malaise (OR: 2.33, 95 % CI [0.99-5.48]), p = 0.013 and anxiety/depression (OR: 0.39, 95 % CI [0.28-0.55], p = 0.019). The overall health perception was 80 points for Whipple (IQR 60-90) vs. 100 points for the control group (IQR 90-100). Conclusions: Patients undergoing a Whipple procedure experience a health perception slightly lower than patients undergoing laparoscopic cholecystectomy. This difference may be associated with increased pain, anxiety/depression and a reduction in their activities of daily life. The administration of the EQ-5D-5L questionnaire to measure quality of life is a friendly tool that used be used routinely to plan activities aimed at improving medical care.