INTRODUCTION: Migrants face numerous risk factors for mental disorders, including stressors and traumatic events during the pre-, peri-, and post-migratory phases. Acculturation stress, a significant post-migratory stressor, can adversely affect mental health during the cultural adaptation process. This study aims to assess the clinical implications of acculturation stress in migrants admitted to a psychiatric intensive care unit, with a focus on identifying predictors of acculturative stress and their impact on clinical outcomes. METHODS: We conducted a retrospective study of 268 immigrant patients hospitalized between 2004 and 2019 at the psychiatric inpatient unit of the University of Foggia. We collected socio-demographic and clinical data using ad hoc schedules and validated assessment instruments, including the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning (GAF), and the Clinical Global Impression (CGI). Diagnoses were based on DSM-IV-TR/DSM-5 criteria. We analyzed associations between demographic and clinical characteristics of patients reporting acculturative stress and those not reporting it, using appropriate statistical methods. RESULTS: The majority of patients were diagnosed with affective (45.1%) or psychotic disorders (31.7%), with 57.1% experiencing their first psychiatric episode. Acculturation stress was reported by 51.9% of patients ( CONCLUSIONS: Acculturation stress is influenced by several socio-demographic factors and is crucial for the full symptomatic remission of migrant patients. Culturally-oriented mental health services, including language and cultural integration programs, are essential in reducing acculturative stress and improving the overall well-being of immigrants.