Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that affects 2% of the general population. Even when the best available treatments are applied, approximately 10% of patients remain severely afflicted and run a long-term deteriorating course of OCD. To determine whether bilateral deep brain stimulation of the nucleus accumbens is an effective and safe treatment for treatment-refractory OCD. The study consisted of an open 8-month treatment phase, followed by a double-blind crossover phase with randomly assigned 2-week periods of active or sham stimulation, ending with an open 12-month maintenance phase. Academic research. Patients Sixteen patients (age range, 18-65 years) with OCD according to DSM-IV criteria meeting stringent criteria for refractoriness to treatment were included in the study. Treatment with bilateral deep brain stimulation of the nucleus accumbens. Primary efficacy was assessed by score change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Responders were defined by a score decrease of at least 35% on the Y-BOCS. In the open phase, the mean (SD) Y-BOCS score decreased by 46%, from 33.7 (3.6) at baseline to 18.0 (11.4) after 8 months (P < .001). Nine of 16 patients were responders, with a mean (SD) Y-BOCS score decrease of 23.7 (7.0), or 72%. In the double-blind, sham-controlled phase (n = 14), the mean (SD) Y-BOCS score difference between active and sham stimulation was 8.3 (2.3), or 25% (P = .004). Depression and anxiety decreased significantly. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported. Bilateral deep brain stimulation of the nucleus accumbens may be an effective and safe treatment for treatment-refractory OCD. isrctn.org Identifier: ISRCTN23255677.