BackgroundInternational students frequently face difficulties that are specific to the typical college experience, in addition to facing other factors of acculturative stress, including cultural differences, language barriers, and comfortability in accommodation.AimThe study aims to measure the prevalence of acculturative stress among first-year international students enrolled at Faculty of Medicine in an Egyptian University and aims to reveal the factors that are associated with acculturative stress in these students.MethodologyA cross-sectional study was conducted on 422 international students in the academic year 2021–2022, using the Acculturative Stress Scale for International Students (ASSIS). The factors associated with acculturative stress were examined using the following criteria: comfort in accommodation, student adjustment to college, language proficiency, and academic pressure.ResultsThis study showed that 28.7% of the international students were “above the warning sign” of acculturative stress (above 109). The major stressors of acculturative stress among international students were the non-specific concerns, homesickness, and perceived discrimination, while the least reported stressors were fear and guilt. International students who scored in the “above the warning sign” in the (ASSIS) were mostly females (35.3%) and non-Arab students (37.8%). Having a friend or a family member living in Egypt significantly reduced the level of acculturative stress. Moreover, the ASSIS total score showed a negative correlation with the scores for overall language proficiency, comfort in accommodation, academic adjustment, and student adjustment to college.ConclusionAcculturative stress among the studied groups is influenced by several factors, including nationality, English and Arabic language proficiency, academic adjustment, and comfort of living. That being said, the most significant stressor is the country of origin, which is defined in terms of nationality or language proficiency. Consequently, resources that ensure the sustainability and growth of international students throughout their educational process must be made available to a multicultural environment in order to support and retain those students.Clinical trial numberNot applicable.