Objective: This study describes the first empirical head-to-head comparison of EQ-5D-3L (3L) and EQ-5D-5L (5L) value sets for multiple countries. Methods: A large multinational dataset, including 3L and 5L data for eight patient groups and a student cohort, was used to compare 3L versus 5L value sets for Canada, China, England/UK (5L/3L, respectively), Japan, The Netherlands, South Korea and Spain. We used distributional analyses and two methods exploring discriminatory power: relative efficiency as assessed by the F statistic, and an area under the curve for the receiver-operating characteristics approach. Differences in outcomes were explored by separating descriptive system effects from valuation effects, and by exploring distributional location effects. Results: In terms of distributional evenness, efficiency of scale use and the face validity of the resulting distributions, 5L was superior, leading to an increase in sensitivity and precision in health status measurement. When compared with 5L, 3L systematically overestimated health problems and consequently underestimated utilities. This led to bias, i.e. over- or underestimations of discriminatory power. Conclusion: We conclude that 5L provides more precise measurement at individual and group levels, both in terms of descriptive system data and utilities. The increased sensitivity and precision of 5L is likely to be generalisable to longitudinal studies, such as in intervention designs. Hence, we recommend the use of the 5L across applications, including economic evaluation, clinical and public health studies. The evaluative framework proved to be useful in assessing preference-based instruments and might be useful for future work in the development of descriptive systems or health classifications.