Background: Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. Aim: To assess the predictive value of MNBI on symptomatic outcomes after anti-reflux therapy. Methods: In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from six channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal oesophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7 and 9 cm, and 15 and 17 cm respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analogue scales) on prospective follow-up after medical or surgical anti-reflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. Results: Of 266 patients, 135 (50.8%) were tested off proton pump inhibitor (PPI) therapy and formed the study cohort (52.1 ± 1.1 years, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiological AET (P < 0.0001), but similar proximal MNBI (P = 0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r = −0.5, P < 0.001), but not proximal MNBI (Pearson's r = 0, P = 0.72). After prospective follow-up (94 patients were followed up for 3.1 ± 0.2 years), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. Conclusions: Distal oesophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following anti-reflux therapy.