Background The vagus nerve has anti‐inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti‐inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long‐term safety, tolerability, and anti‐inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. Methods Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed‐up. Key Results After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C‐reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more “healthy profile”: Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta‐hydroxybutyrate. VNS was well tolerated. Conclusion & Inferences Vagus nerve stimulation appears as an innovative and well‐tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double‐blinded control study.