Background: Political and social developments point at increasing marginalization of Muslim migrants, but little is known about its consequences for the mental health of this particular group. Aim: To explore the relationship between acculturation and psychological distress among first-generation Muslim migrants from Turkey and Morocco in the Netherlands. Methods: A cross-sectional study. Respondents were interviewed in their preferred language. Acculturation was measured with the Lowlands Acculturation Scale (LAS) and psychological distress with the Kessler Psychological Distress Scale (K10). Data were complete for 321 subjects and analyzed with multivariate linear regression. Results: Less skills for living in Dutch society was associated with distress (p = 0.032). Feelings of loss were related to distress among Moroccans (p = 0.037). There was an interaction between traditionalism and ethnic background ( p = 0.037); traditionalism was related to less distress among Moroccans (p = 0.020), but not among Turkish. Finally, there was an interaction by gender among Turks (p = 0.029); conservative norms and values seemed to be related to distress among men (p = 0.062), not women. Conclusion: Successful contact and participation in Dutch society, and maintenance of heritage culture and identity were moderately associated with less psychological distress. Improving mastery of the dominant language in host societies, and allowing migrants to preserve their traditions, might be effective measures in improving the mental well-being of migrants. © The Author(s), 2011.