Research has demonstrated that acculturative stress is an important influence on anxiety and depression in Latinos, however methodological issues limit generalizability of findings. The present study examines Latino subgroup (i.e., Cuban, Puerto Rican, Mexican) differences in the influence of acculturative stress on Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). Secondary data analysis of data from 2,554 Latino immigrants in the National Latino and Asian American Study (NLAAS) included stratified hierarchical logistic regression. The NLAAS collected data via in-person interviews at the participants' homes by bilingual interviewers in the participants’ language of choice. Acculturative stress was significantly related to MDD for Other Latinos (p < .001), and to GAD for Mexicans (p = .040). Results provide empirical evidence for the need to disaggregate Latino subgroups. Subgroup heterogeneity may introduce important contextual factors that should be accounted for when exploring their mental health, particularly when examining acculturative stress.