Background: The goal of this study was to investigate the effects of ethnic origin and acculturation factors on psychiatric problems among immigrant adolescents. One aim was to examine variations in psychiatric problems according to gender and immigrant generation level. Another aim was to explore ethnic group differences in psychiatric problems and acculturation risk and protective factors. Finally, we examined the potential mediating effect of acculturation in the relationship between ethnic origin and psychiatric symptoms. Method: Questionnaire data were collected from 1275 immigrant 10th graders with 11 different ethnic origins. Psychiatric problems were measured by the Strength and Difficulty Questionnaire. Acculturation risk factors involved perceived discrimination and ethnic identity crisis. Protective factors were family values, host and ethnic culture competence. Results: First-generation girls and second-generation boys were identified as particularly vulnerable to psychiatric problems. There was significant variation in psychiatric problems and acculturation between ethnic groups. There was substantial ethnic group-level correlation between emotional and conduct problems, and between discrimination and peer problems. Otherwise, a differentiated pattern of high-scoring ethnic groups emerged across the various symptom and acculturation indices. ANOVAs yielded unique effects on each symptom category of both ethnic group and the acculturation risk and protective factors, undermining the notion of a mediating effect of acculturation. Conclusions: There is a complex pattern of adaptation in cultural context and idiosyncratic relationships between distinct psychiatric symptom groups and socio-cultural factors. Information about the differentiated vulnerability of gender, generation, and ethnic groups to psychiatric morbidity is important to identify groups at special risk, and to produce interventions that are tailored to their needs. Future studies should examine how cultural factors contribute both to resilience and to an increased vulnerability to psychiatric problems.