We examined the prospective associations between nicotine dependence and the likelihood of psychiatric and substance use disorders in the general adult population. Participants came from a nationally representative sample of US adults aged 18 years or older, who were interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001-2002; Wave 2, 2004-2005). The primary analyses were limited to 32,671 respondents (13,751 male (47.9% weighted); mean age of 45 years (SD = 0.18)) who were interviewed in both waves. We used multiple regression and propensity score matching (PSM) to estimate the strength of independent associations between nicotine dependence related to the use of tobacco products at Wave 1 and incident psychiatric disorders at Wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). All analyses adjusted for multiple potential confounders, including childhood (family history of substance use disorders, parental loss, vulnerable family environment), early-adolescence (self-esteem, social deviance, conduct disorder), late-adolescence (education, personality and psychiatric disorders), adulthood (divorce, stressful life events, social deviance, quality of life, history of alcohol or other substance use disorder), and sociodemographic factors. Multiple regression analysis and PSM converged in indicating that nicotine dependence was associated with significantly increased incidence of any psychiatric disorder (OR = 1.39(95%CI:1.20;1.60)), including substance use disorders (OR = 1.91(95%CI:1.47;2.47)), and anxiety disorders (OR = 1.31(95%CI:1.06;1.62)). Population Attributable Risk Proportions were substantial, ranging from 12.5%(95%CI:8.10;17.0) for any psychiatric disorder to 33.3%(95%CI:18.7;48.0) for any other drug use disorder. Supplementary analyses also indicated significant associations between nicotine dependence and persistence of psychiatric and substance use disorders among patients having a disorder at Wave 1. In the general adult population, nicotine dependence is associated with an increased likelihood for several psychiatric and substance use disorders. Given its high prevalence, these findings have important public health implications.