ABSTRACT. Objective: A large Danish birth cohort was used to test the independent and joint effects of perinatal measures associated with premature birth as predictors of the development of alcoholism in male and female subjects. Method: Subjects were born at the Copenhagen University Hospital between 1959 and 1961 (N = 9,125). A comprehensive series of measures was obtained for each of the 8,109 surviving and eligible infants before birth, during birth, shortly after birth, and at 1 year. The adult alcoholism outcome was defi ned as any ICD-10 F10 diagnosis (Mental and behavioral disorders due to alcohol use) or an equivalent ICD-8 diagnosis found in the Danish Psychiatric Central Research Register or the Municipal Alcohol Clinics of Copenhagen by 2007. Results: Multiple perinatal markers of premature birth independently predicted the development of an alcoholism diagnosis in male (n = 310) but not female (n = 138) subjects. Logistic regression modeling with a global prematurity score, adjusted for social status, maternal smoking, and gender, indicated a signifi cant association of prematurity score for males (p < .02), but not females (p = .51), on the risk of developing an alcohol use disorder. Conclusions: The results suggest that neurodevelopmental sequelae of premature birth are associated with gender-specifi c effects on the development of alcoholism in the male baby: small, premature, or growth-delayed male babies appear to be selectively vulnerable to alcoholic drinking years later. The fi ndings implicate neurodevelopmental infl uences in alcoholism pathophysiology in males and suggest the possibility of distinct, gender-specifi c pathways in the etiology of severe problem drinking. (J. Stud. Alcohol Drugs, 72,