Patients receiving treatment for substance dependence frequently endorse high rates of psychological impairment and other measures of reduced quality of life. We conducted a baseline and six-month follow-up study of a series of one hundred and three unselected patients receiving treatment for a substance abuse or dependence problem. Women and patients requiring in-patient detoxification demonstrated the most psychological impairment at baseline, as measured by the mental component summary of the SF-36. Inpatient site of treatment was associated with continued psychological impairment six months following treatment. More aggressive psychiatric and psychological interventions may be indicated for women and for inpatient substance dependence populations.