Context There is consensus in the research literature that substance use disparities exist among sexual minority women and men; however, few studies have examined risk factors that may contribute to these disparities. Aims To compare reports of life-time victimization experiences in a US national sample of adult heterosexual and sexual minority women and men and to examine the relationships between victimization experiences and past-year substance use disorders. Design, participants, measurements The secondary data analyses used 2004?05 (wave 2) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) data collected in structured diagnostic face-to-face interviews in the United States. Substance use disorders (SUDs) were defined according to DSM-IV criteria and included past-year alcohol abuse, alcohol dependence, drug abuse and drug dependence. The sample consisted of 34 653 adults aged 20 years and older; approximately 2% of the respondents self-identified as sexual minority (lesbian, gay or bisexual). Findings Results showed strong associations between victimization and any past-year SUDs and confirmed findings from several previous studies indicating that, compared with heterosexuals, sexual minority women and men are at heightened risk for life-time victimization. However, prevalence of the seven victimization experiences and the degree of association between individual victimization experiences and SUDs varied substantially across sexual minority subgroups. The childhood victimization variables?especially childhood neglect?showed the strongest and most consistent associations with SUDs. Odds of SUDs were generally higher among both female and male respondents, regardless of sexual identity, who reported multiple (two or more) victimization experiences than among those who reported no life-time victimization, suggesting a possible cumulative effect of multiple victimization experiences. Conclusions Higher rates of life-time victimization, particularly victimization experienced in childhood, may help to explain higher rates of substance use disorders among sexual minorities. However, more research is needed to understand better the complex relationships among sexual orientation, victimization and substance use.