Objective: To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy. Methods: This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR. Results: Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 +/- 94.8 vs. 2158 +/- 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Omega was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response. Conclusion: Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients.