Little is known about the effects of substance use on changes in broad personality traits. This 10-year longitudinal study sought to fill this void using a large, representative sample of the Dutch population ( N = 10,872), which provided annual assessments of drug use (tobacco, alcohol, sedatives, soft drugs, ecstasy, hallucinogens, and hard drugs), Big Five personality traits, life satisfaction, and self-esteem. Using multilevel models, we examined the longitudinal associations between drug use and personality both between and within persons. Results indicated that individuals with low levels of conscientiousness, life satisfaction, and self-esteem, as well as high levels of neuroticism, used more drugs on average (between-person effects). In contrast, we found little evidence for personality change following substance use (within-person effects). We discuss these findings in the context of previous empirical and theoretical work and highlight opportunities for future research.