Objective: To report on clinical features, comorbidity, and response to pharmacotherapy in children and adolescents with obsessive-compulsive disorder (OCD) naturalistically followed and treated with serotonin reuptake inhibitors (SRIs). Method: A consecutive series of 94 patients (65 males, 29 females, age 13.6 [+ or -] 2.8 years), referred in the period January 2001-April 2004, diagnosed with a clinical interview (Diagnostic Interview for Children and Adolescents-Revised), and followed for 10 [+ or -] 6 months, were included in the study. Results: Contamination obsessions and washing rituals were associated with less impairment than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as well as symmetry obsessions and ordering-repeating rituals were more frequently comorbid with tic disorders. According to the Clinical Global Impressions-Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment. Nonresponders were more severely impaired and had a higher number of comorbid disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed other medications. Patients receiving SRI monotherapy were less severely impaired; had a later onset of OCD; were at a younger age at the visit, had higher rates of depression and anxiety and lower rates of bipolar disorder, attention-deficit/hyperactivity disorder, and conduct disorder (p < .05).Conclusions: Long-term naturalistic prospective studies in pediatric patients with OCD might represent an important source of information for everyday care regarding the effectiveness of a treatment over extended periods of time under routine clinical conditions. J. Am. Acad. Child Adolesc. Psychiatry, 2005;44(7): 673-681. Key Words: obsessive-compulsive disorder, selective serotonin reuptake inhibitors.