Mental health status and quality of life of female prisoners, the majority of whom are drug-users, was examined as part of a larger, cross-sectional, general healthcare study of the Irish prisoner population. Comparisons were made with drug using and non-drug using male prisoners and females from the general population. Instruments include the GHQ-12 and the WHOQOL-BREF. While their quality of life profile was closer to drug-using male prisoners than other comparison groups, female prisoners still had significantly poorer physical and psychological Quality of Life scores. While poorer quality of life scores may be associated with the more severe drug use patterns of female prisoners it is likely that other factors also contribute. Before resorting to drugs/crime women may have already experienced adversity. There may also be gender differences in response to the combined dimensions of environmental distress. If women are to be imprisoned appropriate comprehensive mental health promotion approaches must address their specific needs.