This pilot study evaluated the effectiveness of enhanced case management for substance abusers with comorbid major depression, which was an integrated approach to care. One hundred and 20 participants admitted to drug treatment who also met Computerized Diagnostic Interview Schedule criteria for major depression at baseline were randomized to enhanced case management (ECM) (n = 64) or treatment as usual (TAU) (n = 56). Both groups were followed up at six and 12 months. Participants' current clinical status across a broad range of domains in the past 90 days was assessed using the Global Appraisal of Individual Needs and included their Depressive Symptom Scale, Homicidal-Suicidal Thought Index, and Mental Health Treatment Index scores. The findings did not reveal any statistically significant effects of ECM on outcome measures. However, in view of the high rates of adverse treatment outcomes among comorbid groups, including suicide, the finding of a clinically significant reduction in homicidal and suicidal thoughts warrants further research; the comprehensive approach to treatment tested may be especially helpful to depressed substance abusers with such ideations.