Mentally ill offenders are disproportionately involved in prison misconduct. Although mental illness is recognized as a risk factor for poor prison adjustment, the additive nature of mental illness co-occurring with substance use disorders has not yet been examined. Using data from the Survey of Inmates in State Correctional Facilities, the authors compared the institutional misconduct experiences of female inmates with co-occurring disorders (CODs) to those for inmates with singular disorders or no disorders. Bivariate and multivariate analyses indicated that the risk of misbehavior was higher for inmates with mental illness combined with a drug dependence/abuse disorder than for inmates with singular disorders, but their disciplinary experiences did not statistically differ. These findings suggest that inmates with CODs may pose a uniquely complex challenge for prison administration, which has important implications for corrections policy and practice. Abstract published by arrangement with Taylor and Francis.