Background: Combined multichannel intraluminal impedance‐pH (MII‐pH) monitoring detects gastro‐oesophageal reflux and identifies acid and non‐acid reflux events. It can be used in patients with persistent symptoms on proton‐pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII‐pH monitoring. Method: A prospectively maintained database identified patients with persistent symptoms of gastro‐oesophageal reflux disease despite PPI therapy who had undergone MII‐pH monitoring and this was cross‐referenced with patients who had undergone fundoplication at this institution. Follow‐up after fundoplication was by periodic telephone interview and review of clinical records. Results: Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7–78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow‐up of 14 (range 7–25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow‐up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months. Conclusion: Patients with a positive symptom index resistant to PPIs with non‐acid or acid reflux demonstrated by MII‐pH monitoring can be treated successfully by laparoscopic Nissen fundoplication. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. A technique worthy of wider evaluation