Purpose. The aim of this study was to evaluate the effectiveness of laparoscopic Nissen–Rossetti fundoplication in patients with gastroesophageal reflux disease (GERD) poorly responsive to standard dose proton pump inhibitor (PPI) therapy. Methods. A total of 35 patients (19 women, 16 men, mean age 44.6 ± 14.01 years) were enrolled. All the patients underwent symptom questionnaires, upper gastrointestinal endoscopy, esophageal manometry, and combined 24-hour esophageal pH and bilirubin monitoring. Following this, the patients with persistent pathological esophageal acid and/or bilirubin exposure underwent laparoscopic antireflux surgery, followed by clinical and instrumental 12-month follow-up. Results. One year after surgery, there was a significant improvement of symptom score, compared with standard PPI dose period (3.54 ± 1.67 vs 20.8 ± 10.9, P < .0001; paired t test) and mean percentage total time acid and bile exposure showed a significant decrease (4.9 ± 2.9 vs 2.03 ± 0.74 and 8.3 ± 3.03 vs 0.84 ± 0.56, P < .0001; paired t test). Conclusions. In patients with GERD poorly responsive to standard PPI dose, laparoscopic Nissen–Rossetti fundoplication appears to be a safe and effective treatment of symptoms, esophageal damage, as well as both acid and bile reflux.