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We sought to compare directly elicited valuations for EQ-5D health states between the US and UK general adult populations.We analyzed data from 2 EQ-5D valuation studies where, using similar time trade-off protocols, values for 42 common health states were elicited from representative samples of the US and UK general adult populations. First, US and UK population mean valuations were estimated and compared for each health state. Second, random-effect models were used to compare the US and UK valuations while adjusting for known predictors of EQ-5D valuations (ie, age, sex, health state descriptors) and to investigate whether and how the valuations differ.Population mean valuations of the 42 health states ranged from −0.38 to 0.88 for the United States and from −0.54 to 0.88 for the United Kingdom, with the US mean scores being numerically higher than the UK for 39 health states (mean difference: 0.11; range: −0.01 to 0.25). After adjusting for the main effects of known predictors, the average difference in valuations was 0.10 (P < 0.001). The magnitude of the difference in the US and UK valuations was not constant across EQ-5D health states; greater differences in valuations were present in health states characterized by extreme problems.Meaningful differences exist in directly elicited TTO valuations of EQ-5D health states between the US and UK general populations. Therefore, EQ-5D index scores generated using valuations from the US general population should be used for studies aiming to reflect health state preferences of the US general public.