Decrease of esophageal mean nocturnal baseline impedance reflects loss of mucosal integrity. It can predict response to anti-reflux therapy. Mean nocturnal baseline impedance after transoral incisionless fundoplication for gastroesophageal reflux disease has never been assessed. The aim of the study is to investigate mean nocturnal baseline impedance and conventional pathophysiological parameters following transoral incisionless fundoplication. Patients prospectively treated by transoral incisionless fundoplication in a single center were retrospectively reviewed regarding 1- and 2-year 24-hour pH-metry and multichannel intraluminal impedance with calculation of mean nocturnal baseline impedance, gastroesophageal reflux disease-health related quality of life and reflux symptom index scores. Thirty-eight and 17/38 patients with 1- and 2-year 24-hour pH-multichannel intraluminal impedance assessment and mean nocturnal baseline impedance's calculation after transoral incisionless fundoplication, respectively, were identified. Mean nocturnal baseline impedance significantly increased up to 2-year follow-up (P = 0.033), along with significant decrease in % of acid exposure time (P = 0.003), gastroesophageal reflux disease-health related quality of life score (P < 0.001), and reflux symptom index (P = 0.008), compared with baseline. The longest orthostatic reflux decreased too, approaching statistical significance (P = 0.054). These significant changes occurred in patients experiencing ≥ 50% reduction of symptom questionnaires' scores ("responders"). Conversely, mean nocturnal baseline impedance worsened and no significant changes of 24-hour pH-multichannel intraluminal impedance metrics were observed in "non-responder" patients (symptom questionnaires' scores decrease < 50%).ConclusionIn patients who responded a significant improvement of mean nocturnal baseline impedance and % acid exposure time was observed up to 2-year follow-up, suggesting that transoral incisionless fundoplication achieves an effective esophageal mucosa healing besides symptom improvement.