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Background: The aim of a rapid response system (RRS) is to improve the timely recognition and treatment of ward patients with deteriorating vital signs The system is based on a set of clinical criteria that are used to assess patient's vital signs on a general ward. Once a patient is evaluated as critical, a medical emergency team is activated to more thoroughly assess the patient's physical condition and to initiate treatment. The medical emergency team included a critical care physician and a critical care nurse., Aim: To assess the effect of an RRS on health-related quality of life (HRQOL)., Methods: Prospective cohort study in surgical patients before and after implementing an RRS. HRQOL was measured using the EuroQol-5 dimensions (EQ-5D) and the EQ visual analogue scale (VAS) at pre surgery and at 3 and 6 months following surgery., Results: No statistical significant effects of RRS implementation on the EQ-5D index and EQ-VAS were found. This was also true for the subpopulation of patients with an unplanned intensive care unit admission. Regarding the EQ-5D dimensions, deterioration in the 'mobility' and 'usual activities' dimensions in the post-implementation group was significantly less compared to the pre-implementation group with a respective mean difference of 0.08 (p = 0.03) and 0.09 (p = 0.04) on a three-point scale at 6 months. Lower pre-surgery EQ-5D index and higher American Society of Anesthesiologists physical status (ASA-PS) scores were significantly associated with lower EQ-5D index scores at 3 and 6 months following surgery., Conclusions: Implementation of an RRS did not convincingly affect HRQOL following major surgery. We question if HRQOL is an adequate measure to assess the influence of an RRS. Pre-surgery HRQOL- and ASA-PS scores were strongly associated with HRQOL outcomes and may have abated the influence of the RRS implementation.