OBJECTIVES:  European countries vary considerably in both lifestyle and healthcare delivery systems, and therefore the impact of a given condition may vary considerably according to country of residence. The current study was conducted to assess the health-related quality of life (HRQoL) decrement in the 5 major markets of the European Union associated with impactful diseases identified by the Centers for Disease Control and Prevention, and whether the burden associated differs by country. METHODS:  : Data were from the 2016 EU5 National Health and Wellness Survey, an internet-based survey of adults 18 and older in France, German, Italy, Spain, and the United Kingdom (EU5; N=80,600). HRQoL was measured with the visual analog score (VAS) from the EQ-5D-5L. The VAS scores of respondents who reported experiencing the condition were compared with those that did not report the condition using t-tests within in each country. Conditions included heart disease, cancer, obesity, osteoarthritis, and diabetes. Nonequivalence testing on the impairment associated with each condition across countries was used to determine whether the impact significantly varied across countries. RESULTS: All five of the conditions were associated with significant (p<0.001) decrements within each country, ranging from a low of 5.0 points on the 0-100 VAS (obesity, Spain) to 16.4 points (osteoarthritis, Germany). Pairwise nonequivalence testing indicated at least one difference in the magnitude of burden associated with heart disease cancer, obesity, and osteoarthritis across the 5 countries. The exception was diabetes, which had considerable impact in all countries (range 9.2 to 12.3 points) but nonequivalence was not shown for any pairwise comparison. CONCLUSIONS:  The impact of well-recognized chronic conditions varies within European countries. Policy makers seeking to optimize the allocation of healthcare resources for the improvement of HRQoL should rely on country-level rather than pan-European studies of disease burden where feasible.