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This study reports findings from two-level growth curve modeling of cigarette smoking and depressive symptoms based on the first three waves of data from a longitudinal study of Indigenous adolescents and their parents/caretakers in the northern Midwest and Canada. The 743 adolescents were aged 10–13 years at Wave 1 and 12–15 years at Wave 3. Over the three years of the study the overall retention rate was 93%. By Wave 3, 39% of the adolescent girls and 25% of the boys had smoked cigarettes in the past 12 months. The growth curve results indicated that smoking increased for both adolescent boys and girls across time. Depressive symptoms were associated with an increase in cigarette smoking for girls but not boys.