Background: The level of acculturation of migrants varies and is associated with variations in mental health. However, this association is complex and may differ among migrant groups. Aim: The aim of this study is to explore the association between acculturation, mental health and treatment effect. Methods: In a longitudinal cohort study of patients treated in specialized mental health facilities, different dimensions of acculturation (skills, social integration, traditions, norms/values and feelings of loss) were explored for Moroccan, Turkish and Surinamese migrants in the Netherlands. Furthermore, the associations between acculturation status and symptom levels, quality of life, care needs and effects of mental health treatment were examined. Data were analyzed with analysis of covariance, correlation analysis and multiple regression analysis. Results: Acculturation status differed among migrant groups. Turkish migrants showed most original culture maintenance (traditions, norms/values), Surinamese migrants showed most participation in Dutch society (skills, social integration), while Moroccan migrants were situated in between. Higher cultural adaptation was associated with less need for care, lower symptom levels and a higher quality of life. Participation significantly predicted lower symptom levels (p<.001) and higher quality of life (p<.001) 6 months after the start of treatment. Conclusion: This study confirms that acculturation status is associated with symptom levels, quality of life and perceived need for care of migrants. Moreover, participation in Dutch society appears to be a favorable factor for treatment effect. It is of importance for professionals in clinical practice to be attentive to this.