Abstract Background The European Health Examination Survey in Luxembourg (EHES-LUX) is a population based survey performed from 2013 to 2015 with the aim to establish baseline information on the general health status of the Luxembourg population aged 25 to 64 years. The paper introduces the study design, recruitment method and representativeness of the sample, and summarizes the sociodemographic characteristics of participants and the prevalence of major health outcomes. Methods EHES-LUX is based on a random sample representative of the population of Luxembourg based on gender, age and district of residence. The sample size of the study was determined to provide accurate prevalence estimates for major chronic conditions. During two visits, data were collected from participants through a questionnaire (personal data, health status and health care), medical examinations (anthropometric measures, electrocardiogram and spirometry) and biological analysis (blood, urine and hair). Means and frequencies were used to describe the general characteristics of the population and a one-way ANOVA to test the representativeness of the sample and the comparability of participants and non-participants. Results A total of 1529 individuals participated in this study (participation rate of 24.1%). Differences between participants and non-participants based on gender, age and district of residence were corrected by sampling weights. The mean age (±SD) of participants was 44.9 (±10.1) years, of which 52.8% were women. Based on clinical measurements, nearly 20% of participants were obese and more than one in three participants were overweight. From measurements (respectively from self-report), 22.0% (respectively 12.2%) were hypertensive, 49.3% (respectively 22.5%) had hypercholesterolemia, 3.5% (respectively 3.7%) had diabetes and 7.6% (respectively 6.0%) had depressive symptoms. Conclusions This nationwide epidemiological study on the general health status of Luxembourg residents provides updated prevalence estimates on a range of ...