Objective: The aim of this study was to examine the relationship between obsessive-compulsive symptoms (OCS) and substance use in patients with a non-affective psychotic disorder. Method: The data were derived from the Genetic Risk and Outcome of Psychosis study. Using the Yale-Brown Obsessive Compulsive Scale, three groups of in- and outpatients with non-affective psychotic disorder (76.6% male, mean age 27.7 years, mean duration of illness 4.5 years) were distinguished: patients without OCS (N = 777), patients with mild OCS (N = 143) and patients with more severe OCS (N = 85). These three groups were compared using various substance use variables, including quantitative substance use variables and severity of substance use [Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) misuse disorders]. Results: We found no statistically significant differences in smoking and other substance use variables between the three patients groups according to the severity of OCS. Conclusions: Our large study sample and detailed comparison of substance use rates strongly adds to the evidence that schizophrenia patients with OCS do not differ in prevalence of substance use compared to patients without OCS. This suggests that in clinical practice, enquiring into (problematic) substance use is relevant in both schizophrenia patients with co-morbid OCS and patients without OCS. © 2013 The Royal Australian and New Zealand College of Psychiatrists.