Abstract Objectives : While treatment is known to improve drug and crime outcomes for opiate users, there is debate in the literature about the longitudinal effects of substance misuse and the comorbidity of mental health problems. We sought to describe and model anxiety and depression outcomes during opiate substance misuse treatment. Methods : The first national, longitudinal treatment outcome study of 404 opiate users entering a new episode of inpatient or outpatient treatment and followed up at one and three years and assessed using the Maudsley Addiction Profile instrument. Results : A total of 404 opiate users were recruited representing approximately 8.2% of all new treatments and 17% of all new methadone treatments at national level in Ireland in 2003. At three years 97% (n = 392) were followed-up. At one year, analysis revealed the odds of experiencing depression was between five and 15 times the odds for opiate users who also used cocaine than non cocaine using opiate users, but this had decreased at three years. At three years those who were drug free, that is, not in treatment and not using illicit drugs, were less likely to experience feeling hopeless about the future than those in treatment or those not in treatment and using, but they were also more likely to experience feeling tense. Those in treatment were more likely to feel lonely. Conclusion : The concurrent misuse of cocaine and other substances during opiate treatment and the stage of the treatment pathway are associated with anxiety and depression among opiate users in treatment. These client factors need to be considered when implementing individualised treatment care plans.