Given that anorexia nervosa (AN) is a life-threatening mental disorder and has poor clinical outcomes, novel effective treatments are warranted, especially for severe and persistent cases. To investigate the safety, feasibility, and clinical outcomes of using deep brain stimulation (DBS) of the nucleus accumbens (NAcc) in treatment-refractory AN patients. A total of 28 women with refractory AN underwent NAcc-DBS and completed this 2-year follow-up study. The clinical outcomes, including body mass index (BMI) and mood, anxiety, and obsessive symptoms, were assessed using a series of psychiatric scales at 6 and 24 months post operation. While no fatalities were reported during this study, 1 patient showed device rejection. The most common short-term side effect observed was varying degrees of pain at the incision sites (n = 22), which usually disappeared 3-4 days following the operation. No severe surgical adverse events were observed. Compared to presurgical levels, significant increases in BMI and improvement in psychiatric scale scores were noted during the 6-month follow-up and were maintained at the 2-year review. Finally, a post-hoc analysis revealed that the NAcc-DBS was less effective for weight restoration in patients with the binge-eating/purge subtype of AN than in those with the restricting subtype (R-AN). Our long-term follow-up study suggests that NAcc-DBS is safe and effective for improving the BMI and psychiatric symptoms of patients with refractory AN. Although NAcc-DBS appears to be more suitable for patients with R-AN, strict inclusion criteria must be applied considering surgery-related complications.