Growing awareness of autism spectrum disorders has increased the demand for diagnostic services in adulthood. High rates of mental health problems have been reported in young people and adults with autism spectrum disorder. However, sampling and methodological issues mean prevalence estimates and conclusions about specificity in psychiatric co-morbidity in autism spectrum disorder remain unclear. A retrospective case review of 859 adults referred for assessment of autism spectrum disorder compares International Classification of Diseases, Tenth Revision diagnoses in those that met criteria for autism spectrum disorder (n = 474) with those that did not (n = 385). Rates of psychiatric diagnosis (>57%) were equivalent across both groups and exceeded general population rates for a number of conditions. The prevalence of anxiety disorders, particularly obsessive compulsive disorder, was significantly higher in adults with autism spectrum disorder than adults without autism spectrum disorder. Limitations of this observational clinic study, which may impact generalisability of the findings, include the lack of standardised structured psychiatric diagnostic assessments by assessors blind to autism spectrum disorder diagnosis and inter-rater reliability. The implications of this study highlight the need for careful consideration of mental health needs in all adults referred for autism spectrum disorder diagnosis.