Emerging evidence suggests that elevated anxiety sensitivity (AS) is associated with substance use disorders. However, prospective evidence regarding this association is currently lacking. The primary aim of the present study was to determine whether AS is involved in the pathogenesis of substance-related psychopathology. A large, nonclinical sample of young adults (N = 404) was prospectively followed for approximately 2 years. AS (i.e., 16-item Anxiety Sensitivity Index total scores) at study entry and gender served as the primary predictor variables. Findings indicated that AS was uniquely associated with the later development of alcohol use disorder diagnoses. Data indicated that gender and AS did not act synergistically to predict alcohol use disorders. These data provide novel evidence for the unique effects of AS as a prospective risk factor in the development of alcohol-related disorders.