OBJECTIVES The aim of the study was to analyse the differences between hypothetical and experience-based EQ-5D value sets. Furthermore, the aim was to evaluate the health economic implications of such differences for policy decisions in health care.  METHODS We studied the differences in hypothetical and experience-based value sets using three different methods: numerical comparison, empirical comparison, and health economic examples. In the numerical comparison, the valuations of all 243 different EQ-5D states and all pure improvements were compared. In the empirical study, a database of 23,925 individuals was used to identify patient groups that could be influenced by the implementation of experience-based value sets. Two hypothetical health economic examples were used to examine the implication of the choice of value set for decision makers. RESULTS The numerical comparison showed that only three health states were assigned a lower QALY-weight in the experience-based value set. The empirical comparison showed that severe conditions were assigned higher values in case of experience-based value set. Furthermore, the health economic examples showed the choice of a value set has an effect on the health economic result.  CONCLUSIONS Shifting to experience-based QALY-weights would increase the estimated level of quality of life in virtually all health conditions. In extension, quality of life enhancing interventions are given higher priority in decision making situations where hypothetical values are used to construct QALY-weights. On the other hand, in situations where experience-based QALY-weights are used, life-prolonging interventions will be prioritised.