European medical schools are recruiting increasing numbers of international students. This study explores the impact of cultural backgrounds and language on the transition of international medical students to the clinical years of their training when they are predominantly based in hospitals and interacting with health professional staff and patients. A mixed-methods study was undertaken, incorporating 31 peer interviews and a focus group discussion and the development and conducting of an online survey (n = 144; 50% response rate). We compared levels of social adjustment and integration between the students on a regional basis. Overall students adjusted well, but there were statistically significant regional differences in social adjustment and integration. The impact of communication difficulties from a language and cultural practice perspective was a dominant challenge highlighted, as was the differences in hospital culture and interprofessional communication norms. International medical students experience many challenges and benefits from studying in a multicultural environment. More nuanced demographic data need to be collected on admission to assist in potentially identifying those who may experience difficulties with academic and daily life transitions. In addition, all students in a multicultural environment would benefit from a program of acculturation for personal and career development.