OBJECTIVES: To model the relationship between the three-level (3L) and the five-level (5L) EuroQol five-dimensional questionnaire and examine how differences have an impact on cost effectiveness in case studies. METHODS: We used two data sets that included the 3L and 5L versions from the same respondents. The EuroQol Group data set (n = 3551) included patients with different diseases and a healthy cohort. The National Data Bank data set included patients with rheumatoid disease (n = 5205). We estimated a system of ordinal regressions in each data set using copula models to link responses of the 3L instrument to those of the 5L instrument and its UK tariff, and vice versa. Results were applied to nine cost-effectiveness studies. RESULTS: Best-fitting models differed between the EuroQol Group and the National Data Bank data sets in terms of the explanatory variables, copulas, and coefficients. In both cases, the coefficients of the covariates and latent factors between the 3L and the 5L instruments were significantly different, indicating that moving between instruments is not simply a uniform re-alignment of the response levels for most dimensions. In the case studies, moving from the 3L to the 5L caused a decrease of up to 87% in incremental quality-adjusted life-years gained from effective technologies in almost all cases. Incremental cost-effectiveness ratios increased, often substantially. Conversely, one technology with a significant mortality gain saw increased incremental quality-adjusted life-years. CONCLUSIONS: The 5L shifts mean utility scores up the utility scale toward full health and compresses them into a smaller range, compared with the 3L. Improvements in quality of life are valued less using the 5L than using the 3L. The 3L and the 5L can produce substantially different estimates of cost effectiveness. There is no simple proportional adjustment that can be made to reconcile these differences.