BACKGROUND: Although data fully support the use of serotonin reuptake inhibitors (SRIs) in the treatment of obsessive-compulsive disorder (OCD), investigations on pharmacotherapy discontinuation during the course of OCD are lacking. This 5-year prospective study sought to better understand the long-term course of SRI utilization among individuals with OCD. METHODS: A total of 252 adult outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. OCD, treated with medication in the community, were examined for discontinuation and resumption of SRIs. Data on weekly OCD symptoms, medications, and dosage changes were obtained annually using the Longitudinal Interval Follow-up Evaluation. RESULTS: During the 5-year follow-up period, 151 patients had at least one trial of an SRI for 12 weeks or more. A total of 110 patients (43.7%) discontinued their medication (i.e. ceased taking medication for =4 weeks) at least once during the follow-up period. In patients symptomatic at the time of discontinuation, the cumulative incidence of worsening of OCD after SRI discontinuation was 9.8%, whereas in patients in partial or full remission at the time of discontinuation, the corresponding cumulative incidence was 33.3%. Among patients with worsening of OCD upon SRI discontinuation, the median time to worsening was 39 weeks. CONCLUSION: This first longitudinal study on the use of SRIs in OCD found that patients who had achieved partial or full remission on SRIs were less likely to discontinue medication, and the cumulative incidence of worsening of OCD after discontinuation was negatively associated with OCD severity at the time of SRI discontinuation.