<b><i>Introduction:</i></b> Cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) has proven its efficacy in randomized controlled trials (RCTs). <b><i>Objective:</i></b> To test generalizability to routine care settings, we conducted an effectiveness study to provide naturalistic outcome data and their predictors. <b><i>Methods:</i></b> Pre-post changes in symptoms and impairment as well as response rates were determined in a naturalistic OCD sample (intention-to-treat, ITT, <i>n</i> = 393). Patients received individual CBT for OCD adopting an exposure-based, non-manualized treatment format. Linear and logistic regression analyses were applied to identify associations of sociodemographic and clinical variables with symptom change. <b><i>Results:</i></b> Effect size in ITT patients amounted to <i>d</i> = 1.47 in primary outcome (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS). Remission rates were 46.3% (ITT), 52.0% (completers), and 18.2% (non-completers). The rates of treatment response without remission, no change, and deterioration in the ITT sample were 13.2, 38, and 3%, respectively. Initial symptom severity, comorbid personality disorder, and unemployment were associated with a poorer outcome, and previous medication with a better outcome. Comorbid depressive and anxiety disorders as well as other clinical or sociodemographic variables showed no effects on symptom change. <b><i>Conclusions:</i></b> Outcomes in this large observational trial in a naturalistic setting correspond to available RCT findings suggesting that CBT for OCD should be strongly recommended for dissemination in routine care. Targets for further research include early prediction of non-response and development of alternative treatment strategies for patients who respond insufficiently.