Background/Aims: Extended wireless pH monitoring (WPM) is used to investigate gastroesophageal reflux disease (GERD) as subsequent or alternative investigation to 24-hour catheter-based studies. However, false negative catheter studies may occur in patients with intermittent reflux or due to catheter-induced discomfort or altered behavior. We aim to investigate the diagnostic yield of WPM after a negative 24-hour multichannel intraluminal impedance pH (MII-pH) monitoring study and to determine predictors of GERD on WPM given a negative MII-pH. Methods: Consecutive adult patients (> 18 years) who underwent WPM for further investigation of suspected GERD following a negative 24-hour MII-pH and upper endoscopy between January 2010 and December 2019 were retrospectively included. Clinical data, endoscopy, MII-pH, and WPM results were retrieved. Fisher’s exact test, Wilcoxon rank sum test, or Student’s t test were used to compare data.Logistic regression analysis was used to investigate predictors of positive WMP. Results: One hundred and eighty-one consecutive patients underwent WPM following a negative MII-pH study. On average and worst day analysis, 33.7% (61/181) and 34.2% (62/181) of the patients negative for GERD on MII-pH were given a diagnosis of GERD following WPM, respectively. On a stepwise multiple logistic regression analysis, the basal respiratory minimum pressure of the lower esophageal sphincter was a significant predictor of GERD with OR = 0.95 (0.90-1.00, P = 0.041). Conclusions WPM increases GERD diagnostic yield in patients with a negative MII-pH selected for further testing based on clinical suspicion. Further studies are needed to assess the role of WPM as a first line investigation in patients with GERD symptoms.