OBJECTIVES: To identify and describe differences in demographics, quality of life, resource utilization, and healthcare attitudes between clinical trials participants and the general population. METHODS: Data for this analysis were obtained from the 2005 National Health and Wellness Survey (NHWS), an annual nationally representative Internet-based study of the health status, healthcare attitudes, and behaviors of adults (age 18+). The current analysis was limited to respondents from France, Germany and the UK reporting a diagnosis of hypertension, high cholesterol, or diabetes (n=8,384). Respondents reported ever participating in a clinical drug trial, demographic, attitudes, resource use, and quality of life (SF-8 summary scores). RESULTS: Across all countries, 6% (n=472) reported ever participating in a clinical drug trial (France, 4%; Germany, 6%; UK, 7%). In all countries, clinical trial participants were older ( France, 59.19 vs. 52.26, p<0.01; Germany, 56.30 vs. 52.64, p<0.01; UK, 59.93 vs. 56.01, p<0.01), and had more frequent physician visits (France, 9.17 vs. 1.01, p=0.01; Germany, 10.27 vs. 7.47, p<0.001; UK, 6.51 vs. 5.60, p=0.03). Clinical trials participants in France and Germany reported lower physical quality of life (France, 42.98 vs. 45.91, p<0.01; Germany, 41.97 vs. 44.11, p=0.01) than the general population. Only trial participants in Germany had lower mental quality of life (47.38 vs. 49.74, p<0.01) and significantly more emergency room visits and hospitalizations. Trial participants in France were less likely to have insurance than the general population (86.41% vs. 94.44%, p<0.01). Clinical trial participants in the UK were more likely than the general UK population to report a preference for prescription vs. OTC medications (50.50 vs. 42.02, p=0.02). CONCLUSION: Clinical trial participants are intrinsically different from the general population. This should be considered in the design and implementation of clinical trials and the generalization of results to the population.