ObjectivesTo investigate the features of patients with laryngopharyngeal reflux (LPR) who did not respond to medical treatment.Study DesignProspective uncontrolled study.SettingMulticenter study.MethodsPatients with LPR at 24‐hour HEMII‐pH monitoring (hypopharyngeal‐esophageal multichannel intraluminal impedance–pH) were prospectively recruited from 3 European university centers. Patients were treated with 3‐ to 6‐month medication (proton pump inhibitor and alginate) and categorized as mild to moderate responders, high responders, or nonresponders according to Reflux Symptom Score (RSS) changes at 6 months posttreatment. The predictive value of the following outcomes was studied: epidemiologic data, HEMII‐pH, gastrointestinal endoscopy findings, baseline RSS and Reflux Sign Assessment, and early therapeutic response (6‐week RSS).ResultsA total of 148 patients completed the evaluations, accounting for 40 mild to moderate responders (20%‐60% RSS changes), 76 high responders (>60% RSS changes), and 32 nonresponders. Nonresponders presented more often with hiatal hernia and lower esophageal sphincter insufficiency when compared with mild to moderate and high responders (P =. 032). Baseline otolaryngologic, digestive, and respiratory RSS and the number of pharyngeal reflux events at the HEMII‐pH were predictive of the 6‐month therapeutic response (P <. 05). The early therapeutic response (6 weeks posttreatment) was predictive of the 6‐month treatment response.ConclusionHiatal hernia and baseline and 6‐week RSS were the most predictive indicators of therapeutic effectiveness in patients with LPR.