Associations of behavioral health risks and healthy behaviors with self-reported health-related quality of life measures were investigated in a Northern Plains American Indian sample. Participants were surveyed in person using the Behavioral Risk Factor Surveillance Survey. The results showed that regular physical activity was significantly associated with better self-reported overall health, fewer mentally unhealthy and activity limitation days in the past 30 days, and with a greater number of good health days. (Contains 6 tables.)