OBJECTIVE: To validate Lyon Consensus criteria for diagnosing gastro-oesophageal reflux disease (GORD) by reflux monitoring. DESIGN: Manual review of impedance-pH tracings from patients with proton pump inhibitor (PPI)-dependent heartburn, evaluated off PPI. Acid exposure time (AET) thresholds defined by the Lyon Consensus and impedance parameters were investigated, namely, total refluxes (TRs), postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI). RESULTS: The study included 488 patients, 178 (36%) with normal (<4%) AET, 89 (18%) with inconclusive (4%-6%) AET and 221 (45%) with abnormal (>6%) AET, alongside with 70 healthy controls. At receiver operating characteristic analysis, area under curve was 0.89, 0.95 and 0.89 for TRs, PSPW index and MNBI, respectively, and threshold values were 40, 50% and 2000 Ω; the 4% physiological AET threshold defined by the Lyon Consensus showed 100% specificity but 63% sensitivity. The thresholds defined for impedance parameters were validated against AET by means of ordered logistic regression, being in concordance with the 4% AET threshold (OR 2.5 for TRs, 18.9 for PSPW index and 5.7 for MNBI). TRs positivity and concordant PSPW index/MNBI positivity were found in 80%-90% of patients in the abnormal AET group, in 73%-74% of cases in the inconclusive AET group and in 28%-40% of cases in the group with normal AET. CONCLUSIONS: Our results show the overall validity of the Lyon Consensus approach to GORD diagnosis. Adding evaluation of impedance parameters, namely, TRs, PSPW index and MNBI to AET appraisal, substantially improves the diagnostic yield of reflux monitoring.