Comorbidity of substance use and psychiatric disorders, particularly depressive disorders, are well established. The impact of comorbidity on treatment outcomes, particularly following short-term inpatient detoxification and medical management units, has yet to be fully explored. This study reviewed 456 records of patients voluntarily presenting for medical management of substance misuse in Sydney, Australia. Documented psychiatric comorbidities and primary substance of misuse were extracted and used to predict length of stay, discharge against medical advice and number of readmissions. Our results showed that psychiatric comorbidity did not significantly predict treatment outcomes, although depression was reported in more than half our cohort, along with elevated rates of Post-traumatic Stress Disorder, anxiety disorders and bipolar affective disorders. Medication non-compliance and primary substance of misuse significantly predicted length of stay and discharge against medical advice. Further research into how specific substances interact and affect specific psychiatric disorders is needed to guide optimal treatment options.