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Endoscopic full-thickness gastroplication by the Plicator instrument has proven to be a safe and effective method to improve symptoms of gastroesophageal reflux disease. This is the first comparative objective data study for endoscopic versus laparoscopic antireflux procedures.In this single-center controlled open trial in 70 adult patients with documented gastroesophageal reflux disease without hiatal hernias, objective and subjective outcome parameters were evaluated prospectively and compared. Patients were randomly assigned to either endoscopic full-thickness gastroplication or laparoscopic antireflux surgery. Patients in the Plicator group received between 1 and 3 transmural-pledgeted sutures to the gastric cardia. Patients in the laparoscopic anti-reflux surgery (LARS) group underwent Nissen or Toupet fundoplication. Esophageal manometry, 24-hour impedance pH monitoring, Gastrointestinal Quality-of-Life Index, and symptom questionnaires were evaluated at baseline and at the 3-month follow-up for significant (P<0.05) changes and differences.Lower esophageal sphincter pressures were increased in the LARS group and unchanged in the Plicator group. Total reflux numbers, acid, nonacid, proximal, upright, and recumbent reflux events were reduced in both groups, significantly more in the LARS group. Reductions in reflux-related esophageal acid scores were significant only in the LARS group. Similar improvements of Gastrointestinal Quality-of-Life Index were found in both groups. General and gas-related symptom scores were comparably reduced. Greater Reductions in reflux-specific symptom scores were found after LARS. Bowel dysfunction symptom scores were lower after LARS.Improvements in the general subjective outcome parameters were similar after endoscopic full-thickness gastroplication compared with LARS despite a stronger reflux control provided by LARS. More effective relief of reflux-related symptoms favors LARS, and differences in side effect symptoms favor endoscopic full-thickness gastroplication.