The validation of the assessment of depression across ethnic groups is critical yet deficient for American Indian (AI) adults. Therefore, we assessed the psychometric properties of the Center for Epidemiological Studies-Depression (CES-D) in AI elders and tested differences in depression constructs between gender. Participants were 817 AI adults (68% women), mean age 73.2 years (SD = 6.1, range: 64-95) for women and 72.6 years (SD = 5.3, range: 65-90) for men., in the Cerebrovascular Disease and Its Consequences in AIs Study. We evaluated the factor structure of the 20-item and 12-item CES-D and tested measurement invariance between gender. Results demonstrated a poor fit for the 20-item CES-D and partial gender measurement invariance of the 12-item CES-D. AI female elders had significantly higher depression levels than AI male elders on the Depressed Affect subscale, the Somatic Symptoms subscale, and the Well-Being (reverse-coded) subscale. Further replication is needed, and we recommend future psychometric work with the 12-item CES-D with AI elders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).