No group is more at-risk for tobacco-related health disparities than are American Indian youth. Little is known about their readiness to quit smoking and the extent to which cessation programs may require cultural tailoring related to recruitment, implementation, or content. This study identifies unique characteristics of American Indian teen smokers who enrolled in a school-based smoking cessation program, Not On Tobacco (called N-O-T). Using data from N-O-T intervention trials conducted in North Carolina between 2001 and 2004, the present study (a) describes the characteristics of American Indian participants (n = 91); (b) determines if basic demographics and smoking history affect intervention readiness; and (c) compares findings with non-Native participants (n = 138) enrolled in N-O-T within the same state. Upon enrollment, 80% of the sample reported that they planned to quit smoking in the next 1-6 months. We found significant differences between American Indian and non-Native youth on smoking history, with non-Natives smoking with greater intensity and frequency. Contrary to previous reports, American Indian youth in this study smoked with less intensity and were more ready to quit smoking than non-Native youth. Results reveal previously unreported characteristics of American Indian teen smokers. Study findings may advance the development of effective marketing, recruitment, and programming among American Indian teen smokers into cessation programs, particularly N-O-T, which is the only teen smoking cessation program which includes an adaptation specifically for American Indians.