Abstract Background No previous study has examined the prevalence of cardiovascular risk factors and explored the influence of immigration status and acculturation on overweight/obesity among the Portuguese immigrants to Luxembourg. Our objectives were to (1) compare the prevalence of cardiovascular risk factors between native Luxembourgers and Portuguese immigrants, (2) examine the relationship between immigrant generation status, proportion of life spent in Luxembourg and language proficiency or preference (as proxy variables of acculturation) and overweight/obesity among Portuguese immigrants, and (3) elucidate the role of underlying socioeconomic, behavioral and dietary factors in overweight/obesity differences among the two populations. Methods Recent national cross-sectional data from ORISCAV-LUX survey 2007–2008, composed of 843 subjects were analyzed. Overweight/obesity was defined as body mass index (BMI) >25kg/m 2 . Acculturation score was measured by using immigrant generation status, proportion of life spent in Luxembourg, and language proficiency or preference. Univariable and multivariable logistic regression analyses were performed to examine the association between acculturation markers and overweight/obesity. Further, a series of successive models were fitted to explore the separated and added impact of potential mediators (socioeconomic status, physical activity, dietary factors) on overweight/obesity among Luxembourgers and Portuguese immigrants. Results Compared to Luxembourgers, Portuguese immigrants of first and second generation were younger and currently employed. About 68% of first generation Portuguese had only primary school, and about 44% were living below poverty threshold. Although the cardiovascular risk factors were comparable, Portuguese immigrants were more frequently overweight and obese than Luxembourgers, even after age and gender standardization to the European population. Overweight/obesity was significantly higher among Portuguese of first generation compared to second ...