Purpose We evaluated the long-term medical and economic benefits of vagus nerve stimulation (VNS) therapy for 704 adults and children with epilepsy. A pre–post analysis was conducted using Hospital Episode Statistics (HES) data (April 2008–July 2014). Seven hundred and four patients with epilepsy diagnoses (ICD-10 G40.x or G41.x), one or more procedures for vagus nerve stimulator implantation, and six or more months of available HES data pre- and post-VNS were selected. The pre-VNS period averaged 39.1months. The post-VNS period extended from implantation to device removal, death, or study end (up to six years), with a mean duration of 36.4months. Incidence rate ratios (IRRs) and cost differences (£2014) were estimated. Mean age was 28.3years. Results Inpatient admissions decreased post-VNS compared with pre-VNS (adjusted IRR=0.81, P<0.001). Overall, outpatient consultations increased post-VNS compared with pre-VNS (adjusted IRR=1.34, P<0.001). However, outpatient consultations exhibited a decreasing trend in the post-VNS period (adjusted IRR=0.96, P<0.001), suggesting that much of the increased outpatient activity in the post-VNS period relates to follow-up management of the VNS device in the immediate period following implantation, with comparable outpatient resource burden at 36months post-VNS. No significant changes in clinical events were observed; however, average epilepsy-related medical costs were lower post-VNS than pre-VNS (adjusted cost difference −£110 quarterly, P=0.001). Conclusions Vagus nerve stimulation is associated with increased outpatient resource utilization and decreased inpatient admissions, with a reduction in long-term epilepsy-related medical costs post-implantation.