Background/objective: Despite the high comorbidity of substance misuse and schizophrenia, few large scale British studies have looked at symptom profile and outcome in this population. The aim of this study was to use data on substance use among subjects with schizophrenia collected in a randomised controlled trial, validated for the purpose of this study, to see if there are differences between substance users and non users on a variety of outcome measures. Method: 1. A sample of subjects in the CUtLASS study were interviewed using the SCID to determine whether SCID-diagnosed substance misuse disorders corresponded to substance misuse categories generated in the CUtLASS study from casenote review. 2. Substance users were compared with non users on a variety of outcome measures. Results: 1. Two CUtLASS categories, no substance use and major substance use, could be validated against SCID diagnoses; the third category, minor use, could not be validated. 2. Substance misusers were more likely to be young men. There were no significant differences between users and non users for positive and negative symptoms, quality of life, number of previous hospitalisations, extrapyramidal side effects or medication compliance. Drug users were younger at age of first treatment than non users. Alcohol users had more depressive symptoms than non users. Substance users had more negative attitudes towards prescribed medication, although this effect disappeared when age and gender were controlled for. Non compliance was associated with more severe psychopathology, and a worse quality of life. Conclusion: Substance misuse did not seem to confer the adverse outcomes that previous studies suggest.