BACKGROUND AND AIMS: The optimal position for pH electrode placement in the diagnosis of gastroesophageal reflux disease (GERD) is unknown. The aim of this study was to evaluate the discriminatory power of targeted pH recording immediately above the squamocolumnar junction (SCJ) and to compare the results with those obtained by simultaneous recording at the conventional level for pH monitoring. SUBJECTS AND METHODS: Sixty-two patients with typical reflux symptoms and 49 asymptomatic volunteers underwent 48-h simultaneous wireless pH monitoring with two endoscopically placed pH recording capsules, one immediately above the SCJ and one at the traditional position, 6 cm above the SCJ. The diagnostic accuracy, sensitivity, and specificity of pH monitoring at the two levels were analyzed using receiver operating characteristics (ROC) curves. RESULTS: Of the 62 patients (39 men and 23 women, median age 48 yrs), 32 patients had erosive esophagitis and 30 had no endoscopic evidence of mucosal injury. Analysis of the area under the ROC curve (AUC) indicated that the total percent time with pH<4 for the entire 48-h period was the parameter that best distinguished GERD patients from controls. pH monitoring performed directly above the SCJ significantly increased the number of patients correctly classified with GERD compared to standard electrode placement. With a predefined test specificity of 90%, pH monitoring immediately above the SCJ increased the sensitivity of the test from 63% to 86% in all patients, from 78% to 97% in patients with esophagitis and from 47% to 73% in patients with no esophagitis. CONCLUSIONS: Compared to standard electrode placement, wireless pH recording immediately above the SCJ improved the diagnostic performance of esophageal pH monitoring in patients with GERD.