This study was the first to examine the factor structure, measurement invariance, and criterion-related evidence for the construct validity of the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2000) in an Asian American sample. Multigroup confirmative factor analyses were carried out in a community sample of adults of Asian ethnic descent (N = 624; M = 41.47 years, SD = 13.28) across ethnicity (Chinese, Filipinx, and Vietnamese), nativity status (U.S.-born and Asian-born), and gender (female and male) to test a priori competing models and measurement invariance. Results of bifactor analyses and ancillary estimates provided strong evidence for the general factor of the BSI-18. Invariance tests indicated that BSI-18 items were interpreted in a similar fashion, and responses could be meaningfully compared across ethnicity, gender, and nativity samples. In addition, theory-consistent correlations with self-esteem and racial microaggression experiences provided criterion-related evidence for the BSI-18. Results may not generalize to other Asian American groups (e.g., South Asians, Asian elders, and clinical samples), and researchers are strongly encouraged to conduct further internal structure analyses of the BSI-18 among Asian American populations. In conclusion, we recommend calculation and interpretation of the BSI-18 total score as a measure of general psychological distress for Asian American populations.