Columnar-lined epithelium with specialized intestinal metaplasia of the esophagus (i.e., Barrett's esophagus) is a premalignant condition caused by chronic gastroesophageal reflux disease. Progression of intestinal metaplasia may be avoided by antireflux surgery, whereas regeneration of esophageal mucosa could be achieved by endoscopic argon plasma coagulation (EAPC). The aim of this prospective study was to show the early results of a combination of EAPC and antireflux surgery. Thirty patients with Barrett's esophagus were treated between August 1996 and December 1999. Regeneration of esophageal mucosa was achieved with several sessions of EAPC under general anesthesia. All patients were receiving a double dose of proton pump inhibitors. Endoscopic follow-up was performed 6 to 8 weeks after the last session. Antireflux surgery (Nissen [n = 26] or Toupet [n = 4] fundoplication) followed complete regeneration of the squamous epithelium in the esophagus. One year after laparoscopic fundoplication and EAPC follow-up with endoscopy and quadrant biopsies of the esophagus, 24-hour pH monitoring and esophageal manometry were performed. All 30 patients showed complete regeneration of the squamous epithelium after a median of two sessions (range 1 to 7) of EAPC. Twenty-two patients underwent 1-year follow-up studies. All showed endoscopically an intact fundic wrap. Recurrence of a 1 cm segment of Barrett's epithelium without dysplasia was present in two patients, both of whom had recurrent acid reflux due to failure of their antireflux procedure. Our results indicate that the combination of EAPC and antireflux surgery is an effective treatment option in patients with Barrett's esophagus with gastroesophageal reflux disease. Long-term follow-up of this therapy is necessary to evaluate its effect on cancer risk in Barrett's esophagus.