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Aims To examine whether there is evidence of an independent association between childhood sexual abuse (CSA) and nicotine disorder in youth and to explore the mechanisms underlying this association in a prospective cohort study. Design Birth cohort study followed-up to 21 years. Setting One of two major obstetric hospitals in Brisbane, Australia. Participants The Mater-University of Queensland Study of Pregnancy involves a prospective birth cohort from a population-based sample involving 7223 singletons whose mothers were enrolled between 1981 and 1984 at the first antenatal visit. The present cohort consisted of a subgroup of 2571 youth who completed the life-time version of the Composite International Diagnostic Interview—computerized version (CIDI-Auto) at the 21-year follow-up. Measurements Nicotine disorder was measured based on Diagnostic and Statistical Manual version IV (DSM-IV) diagnostic criteria and measures of CSA, including retrospective self-reports of rape, were obtained at 21 years. Results Of 2571 young adults, 16.6% met the criteria for either dependence (12.8%) or withdrawal (8.5%). Non-penetrative sexual abuse was reported by 15.5% of respondents and 8.0% reported penetrative sexual abuse. For any types of sexual abuse including non-penetrative, penetrative and self-reported rape before age 16 years, young adults had significantly higher rates of nicotine disorder than young adults who did not experience CSA. This relationship was independent and appeared direct after adjustment for a range of potential confounding and mediating factors. Conclusions This study shows that CSA is associated with young adult nicotine disorder. The results extend the public health significance of findings in this area and highlight the importance of not only intensifying public health efforts to address substance use problems among those who have experienced CSA, but of early intervention, so that emerging risky behaviours may be targeted in the earliest stages. [ABSTRACT FROM AUTHOR]