Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n=11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years).