Tobacco and alcohol are often used in tandem over time, but specific predictors of course and patterns of course over time need explication. We examined differences in alcohol and tobacco course among an adolescent population as they transitioned into young adulthood across a 17-year period. Data came from participants (n = 303 for ages 15-21, n = 196 for ages 21 to 32; 52% female and 54% female, respectively) enrolled in the Amsterdam Growth and Health Longitudinal Study, an epidemiologic investigation examining disease across the life span. We utilized parallel latent growth modeling to assess the impact of sex, personality traits, cholesterol, blood pressure, and body mass index (BMI), on initial status and linear change over time in course of tobacco and alcohol. Females reported less alcohol use at adolescent baseline (β = -21.79), less increase during adolescence (β = -7.92, p < .05), slower decrease during young adulthood (β = 4.67, p < .05), and more rapid decline in tobacco use during young adulthood (β = -70.85, p < .05), relative to males. Alcohol and tobacco use baseline status' and change over time were all significantly associated with one another during both adolescence and young adulthood (p < .05; aside from alcohol baseline and slope during young adulthood). Effects of BMI, cholesterol, blood pressure, and personality traits were also observed on tobacco and alcohol course. In light of the strong, but sex dependent relationship between alcohol and tobacco course, particularly from ages 15 to 21, prevention efforts to curb heavy alcohol and tobacco use should consider targeting course taking into account biological sex and other notable covariates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).