This study examined associations between alcohol misuse and childhood maltreatment and out-of-home placement among urban lesbian, gay, and bisexual (referred to as two-spirit) American Indian and Alaska Native adults. In a multi-site study, data were obtained from 294 individuals who consumed alcohol during the past year. The results indicated that 72.3% of men and 62.4% of women engaged in hazardous and harmful alcohol use and 50.8% of men and 48.7% of women met criteria for past-year alcohol dependence. The most common types of childhood maltreatment were physical abuse among male drinkers (62.7%) and emotional abuse (71.8%) among female drinkers. Men and women reported high percentages of out-of-home placement (39% and 47%, respectively). Logistic multiple regressions found that for male drinkers boarding school attendance and foster care placement were significant predictors of past-year alcohol dependence. For female drinkers, being adopted was significantly associated with a decreased risk of past-year drinking binge or spree. Dose-response relationships, using number of childhood exposures as a predictor, were not significant. The results highlight the need for alcohol and violence prevention and intervention strategies among urban two-spirit individuals.