Purpose: There are significant gaps in the literature on the prevalence of mental health problems and associated needs in Vietnam. A thorough understanding of culture-specific expressions of psychiatric distress is vital for the identification of the mental health needs of a community, and more research on the development and evaluation of culturally-sensitive mental health assessments is warranted. This study aims to evaluate the psychometric properties of the World Health Organization 20-item Self-Reporting Questionnaire (SRQ-20) in an epidemiologic study of Vietnamese adults. Methods: A latent variable modeling approach investigated the underlying factor structure of the SRQ-20 items. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted on SRQ-20 item-level data gathered from 4980 participants. Results: Based on scree plots and EFA results, two latent structures were deemed plausible and were subsequently subjected to further modeling. A bi-factor model (BFM) and a correlated three-factor model solution (Negative Affect, Somatic Complaints, and Hopelessness) provided reasonable fits. The BFM specifies a single dominant General Distress factor (all SRQ-20 items) with orthogonal group factors for the subsets of items: Negative Affect (9 items), Somatic Complaints (8 items), and Hopelessness (3 items). This model fit the data as well or better than the three-factor model. Results also showed differences in endorsement rates of SRQ-20 items among males and females. Conclusions: Study results provide an evaluation of the psychometric properties of a commonly used screening tool and offer insight into the presentation of mental distress in a representative sample of Vietnamese adults.