Objective: Poor emotion regulation is associated with risk for cardiovascular disease. However, much of this research is conducted in primarily White samples, thus limiting our understanding of this relationship in other racial/ethnic groups. American Indians (AIs) are uniquely and disproportionately at risk for cardiovascular disease. As such, the present study aimed to examine the relationships between emotion regulation strategies and ambulatory cardiovascular activity in an entirely AI sample. Methods: The sample consisted of 100 AI adults living on a tribal reservation. Emotion regulation strategies (expressive suppression, cognitive reappraisal) were assessed via the Emotion Regulation Questionnaire. Using ecological momentary assessment, daily measurements of psychological stress and ambulatory cardiovascular activity were taken during a 7-day monitoring period. Statistical analyses included bivariate correlations, hierarchical linear regression models, and mediation models. Results: Expressive suppression was associated with higher systolic and diastolic blood pressure, as well as higher pulse rate. In contrast, cognitive reappraisal was associated with lower systolic and diastolic blood pressure, lower pulse rate, and lower average daily psychological stress. These results remained statistically significant after adjusting for age, sex, body mass index, anxiety, depression, and early life trauma. In addition, psychological stress mediated the associations between blood pressure and cognitive reappraisal, but not expressive suppression. Conclusions: These results provide preliminary evidence for divergent associations of two emotion regulation strategies with cardiovascular activity and psychological stress in an AI community. Modifying health interventions to include training in effective emotion regulation may be beneficial.