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In patients presenting with uncomplicated gastroesophageal reflux disease, nonresponders to medical treatment are not viewed as good candidates for surgical treatment. Considering preoperative response to medical treatment and quality of life, this study aimed to predict outcome following laparoscopic Nissen fundoplication.In an academic center, 35 consecutive patients presenting with a gastroesophageal reflux disease requiring a laparoscopic Nissen fundoplication were prospectively included; 16 patients were nonresponders. Using Gastro-Intestinal Quality-of-Life Index score, quality of life was measured preoperatively and postoperatively at each visit (3, 6, 12, 24, 48, and 72 mo) and was compared between responders and nonresponders.No postoperative complication was recorded. Preoperative score was significantly lower in nonresponders (P<0.02) and digestive symptoms and dietary modifications were more important in nonresponders. The score increased in nonresponders after 48 and 72 months, but this improvement was nonsignificantly lower than in responders (P=0.4). In nonresponders, 6 years after the procedure, all symptoms improved. In responders, dysphagia and gastroesophageal reflux symptoms significantly improved.Laparoscopic Nissen fundoplication seems to improve the quality of life in nonresponders without equaling to responders results, especially because of digestive symptoms. Laparoscopic Nissen fundoplication may be considered as a therapeutic option in selected and informed nonresponder patients.