It is widely accepted that laryngopharyngeal reflux requires more aggressive and prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness, cough, and globus pharyngeus, are slower to resolve than esophageal symptoms, such as heartburn and regurgitation. The aim of this was to provide empirical evidence to support this observation and to carry out a detailed investigation of the differences between these symptoms. Forty-five patients with laryngopharyngeal and esophageal symptoms received acid-suppression therapy that involved the continuous administration of a proton-pump inhibitor for up to 6 months. We investigated the differences in response to acid-suppression therapy between patients suffering from laryngopharyngeal and esophageal symptoms, respectively, who received upper gastrointestinal endoscopy and were assayed for serum Helicobacter pylori antibodies. The significance of the rate of symptom improvement was estimated by Kaplan-Meier analysis and the logrank test. Laryngopharyngeal symptoms improved significantly more slowly than esophageal symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the start of acid suppression; P = 0.003). These differences were observed both in patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative patients (P = 0.001).