Background: A history of separation anxiety disorder (SAD) is frequently reported by patients with obsessive-compulsive disorder (OCD). The purpose of this study was to determine if there are clinical differences between OCD-affected individuals with, versus without, a history of SAD. Methods: Using data collected during the OCD Collaborative Genetic Study, we studied 470 adult OCD participants; 80 had a history of SAD, whereas 390 did not. These two groups were compared as to onset and severity of OCD, lifetime prevalence of Axis I disorders, and number of personality disorder traits. Results: OCD participants with a history of SAD were significantly younger than the non-SAD group (mean, 34.2 versus 42.2 years; Po.001). They had an earlier age of onset of OCD symptoms (mean, 8.0 versus 10.5 years; Po.003) and more severe OCD, as measured by the Yale-Brown Obsessive Compulsive Scale (mean, 27.5 versus 25.0; Po.005). In addition, those with a history of SAD had a significantly greater lifetime prevalence of agoraphobia (odds ratio (OR) 5 2.52, 95% confidence interval (CI) 5 1.4-4.6, Po.003), panic disorder (OR 5 1.84, CI 5 1.03-3.3 Po.04), social phobia (OR 5 1.69, CI 1.01-2.8, Po.048), after adjusting for age at interview, age at onset of OCD, and OCD severity in logistic regression models. There was a strong relationship between the number of dependent personality disorder traits and SAD (adjusted OR 5 1.42, CI 5 1.2-1.6, Po.001). Conclusions: A history of SAD is associated with anxiety disorders and dependent personality disorder traits in individuals with OCD. Depression and Anxiety 28:256-262, 2011.