This study aimed to evaluate the long-term course of obsessive-compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving at least partial remission from obsessive-compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. For subjects who achieved at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state, and of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities. The development of alternative strategies is needed to improve the treatment approaches for treatment-resistant OCD patients.