OBJECTIVES: Treatment-resistant depression (TRD) is a debilitating condition with a significant impact on patients and carers, and a substantial burden on health care budgets. The objective of this analysis was to evaluate the budget impact of introducing vagus nerve stimulation (VNS) for TRD in England. METHODS: The analysis was based on population estimates from a Clinical Commissioning Group (CCG) in England (N=366,000). Patient records from 5 GP practices were analysed based on ICD10 codes, age, history of depression and referrals, to determine a group of patients eligible for VNS. Estimates of the burden of TRD on the NHS regarding hospital admissions and psychiatrist visits were derived from an analysis of Hospital Episode Statistics (HES). Unit costs were obtained from the NHS reference costs. Several sales forecast scenarios were explored. RESULTS: The cost of VNS to the NHS, including the device, implantation procedure, programming, monitoring, and battery replacement, was estimated at under £15,000 per patient. The hospital length of stay for the average TRD patient was estimated at 40 days per completed episode (range: 6 – 68 days); reduced to 27 days after implantation. The average annual number of booked outpatient appointments was 11 (4 – 18); reduced to 5 appointments with VNS. Using forecasts that reflected an exponential growth in the adoption of VNS, the net budget impact was estimated at a total of £1.5 million over the years 2019 to 2023. This estimate corresponded to just over £2000 for each patient implanted with VNS. If past UK adoption rates of VNS and deep brain stimulation for other indications were used to forecast instead, the introduction of VNS would produce total savings in 2023. CONCLUSIONS: When considering all relevant costs and resource use, the introduction of VNS in NHS England can be a long-term cost-saving option for patients suffering with TRD.