IntroductionImpedance-pH testing (MII-pH) while patients are on acid suppression medications is frequently used to evaluate persistent reflux symptoms. The aim of this study was to determine whether MII-pH on medications can reliably identify patients with gastroesophageal reflux disease (GERD) as defined by pathologic esophageal acid exposure off medications, and to determine if there is a threshold of total reflux episodes on medications where pH testing off medications may be unnecessary. MethodsA retrospective review identified all patients between 1/2010 and 4/2017 who underwent MII-pH testing on PPI medications and subsequently had pH testing off medications. GERD was defined on pH testing off medications by an abnormal DeMeester Score (DMS) and on MII-pH on medications by ≥ 48 total reflux episodes. Patients with an abnormal DMS by MII-pH on medications were excluded. ResultsThere were 71 patients, (22 males; 49 females), with a median age of 52 years. Based on ≥ 48 total reflux episodes by MII-pH testing on medications, 42 patients (59%) had GERD. When tested off medications, an abnormal DMS was present in 44 patients (62%). Among those with GERD based on impedance testing on medications, 31% did not have GERD based on pH testing off medications. Further, in the 29 patients with ≤ 48 total reflux episodes on MII-pH (normal test), 15 patients (52%) had pathologic acid exposure off medications. When there were > 73 reflux events with MII-pH on medications, all 15 patients in our series had pathologic acid exposure on pH testing off medications. ConclusionMII-pH testing on medications in patients with refractory GERD symptoms does not reliably correlate with a diagnosis of GERD as defined by pathologic esophageal acid exposure off medications. The commonly used abnormal MII-pH test value of ≥ 48 total reflux episodes is not validated and should not be used. However, in our series, patients with > 73 total reflux episodes had a high likelihood of having pathologic acid exposure off medications. Overall, the preferred strategy to evaluate patients with persistent GERD symptoms on acid suppression therapy should be pH testing off medications.