Objectives: This study evaluated the characteristics of reflux in patients with laryngopharyngeal reflux (LPR) refractory to proton pump inhibitor (PPI) therapy using the 24-h multichannel intraluminal impedance (MII)-pH monitoring. Design: Prospective cohort study. Setting: A tertiary care otolaryngology clinic. Participants: Patients with suspected LPR underwent 24-hour MII-pH monitoring and were prescribed high-dose PPI twice daily. One-hundred and eight patients followed up for at least 2 months were enrolled. Main outcome measures: Patients with suspected LPR showing more than one proximal reflux episode were considered to have LPR. Patients with LPR showing ≥50% decrease in the follow-up reflux symptom index (RSI) score compared to the pre-treatment RSI score during treatment periods were defined as responders; others were defined as non-responders. Various parameters in the 24-h MII-pH monitoring between non-responders and responders with LPR were compared using Student’s t-test. Results: Of 108 patients with suspected LPR, 80 were diagnosed with LPR. Patients with LPR were categorized as non-responders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in MII parameters were significantly higher in responders than in non-responders (p = 0.0040 and 0.0216, respectively). The proximal all reflux time >0.000517% was a better cut-off value to predict responders with LPR compared to the proximal longest reflux time >0.61 min (sensitivity + specificity: 1.317 vs. 1.291). Conclusions: The proximal all reflux time can be helpful to predict the response to PPI therapy and establish a personalized therapeutic scheme in patients with LPR.