Objectives. To better understand patterns of initiation among American Indians we examined age-related patterns of smoking initiation during adolescence and young adulthood in 2 American Indian tribes. Methods. We used log-rank comparison and a Cox proportional hazard regression model to analyze data from a population-based study of Southwest and Northern Plains American Indians aged 18 to 95 years who initiated smoking by age 18 years or younger. Results. The cumulative incidence of smoking initiation was much higher among the Northern Plains Indians (47%) than among the Southwest Indians (28%; P<.01). In the Southwest, men were more likely than women to initiate smoking at a younger age (P<.01); there was no such difference in the Northern Plains sample. Northern Plains men and women in more recent birth cohorts initiated smoking at an earlier age than did those born in older birth cohorts. Southwest men and women differed in the pattern of smoking initiation across birth cohorts as evidenced by the significant test for interaction (P=.01). Conclusion. Our findings underscore the need to implement tobacco prevention and control measures within American Indian communities.