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ABSTRACT: Although the first laparoscopic Nissen fundoplication was performed almost two decades ago, division of the short gastric vessels is still controversially discussed. The aim of this prospectively randomized trial was to evaluate the clinical and functional outcome following laparoscopic Nissen fundoplication with division versus saving of the short gastric vessels during short- and long-term follow-up. Forty-one consecutive patients (30 men, 11 women) with gastroesophageal reflux disease were allocated to undergo Nissen fundoplication without division (group 1, n = 19) or with division (group 2, n = 22) of short gastric vessels. All patients were evaluated prior to and at 6 months as well as 5 years following fundoplication. Tests included endoscopy, barium swallow, 24-h pH monitoring, and esophageal manometry. Gastroesophageal reflux disease (GERD) symptoms were evaluated and a gastrointestinal quality-of-life index was calculated. Preoperative symptoms such as heartburn (84/86%), regurgitation (79/86%), pulmonary symptoms (47/45%), dysphagia (11/32%), chest pain (16/9%), and globus sensation (21/27%) were seen in groups 1 and 2, respectively. In group 1 regurgitation and mild dysphagia were seen in 7 and 26% of patients, respectively, at 5 years. In group 2 the rate of dysphagia decreased from 32 to 17% during short-term follow-up, but increased thereafter to 18%. Reflux esophagitis (preoperative rates: group 1, 74%; group 2, 59%) disappeared in all patients after fundoplication. Mean operative time (group 1, 109 min versus group 2, 125 min; p < 0.05) and mean blood loss (group 1, not measurable; group 2, 25 ml; p < 0.05) showed statistically significant differences. DeMeester score improved in group 1 from 26.6 to 2.2 and in group 2 from 24.7 to 2.5 at 5-year follow-up (p = 0.02). Lower esophageal sphincter (LES) resting pressure returned to normal values (group 1, 23.9 mmHg; group 2, 24.6 mmHg; p < 0.007) with regular relaxation. Quality-of-life index was high in both cohorts, without statistically significant differences between the two groups. Routine division of the short gastric vessels during Nissen fundoplication in the followed patient group yields neither functional nor clinical advantages in short- or long-term follow-up.