First generation college students (FGCSs) may undergo challenging cultural transitions as they acculturate to higher education. Such challenges may include perceived loss of home ties, navigating unfamiliar social rules, and academic acculturative stress. The Academic Acculturative Stress Scale (AAS Scale) was designed to measure these experiences of FGCSs. The sample was comprised of undergraduates at a large public university. Items were created and factor analyzed to evaluate content validity. Mean AAS Scale scores were compared using a 2 (FGCS status) X 2 (gender) factorial analysis of variance. Correlations with students' reported social support, self-esteem, life satisfaction, and depressive symptomatology evaluated criterion validity. A significant two-way interaction for FGCS status and gender for AASS showed that FGCS women reported doing worse than did non-first-generation students, while FGCS men said they were doing better compared to others. Future research should evaluate support needs of FGCS women for successful degree completion.