Background Chronic cough is considered to be part of the gastroesophageal reflux disease (GERD) spectrum. However, the response rate to standard dose proton pump inhibitors (PPI's) is poor. Our aim was to evaluate the response rate of chronic cough to an extended course of high dose PPI's and to identify predictors of treatment response. Methods This prospective study included adult nonsmoking patients with chronic cough, normal spirometry, normal upper endoscopy and with no evidence of postnasal drip (PND). Treatment consisted of high dose PPI's (esomeprazole, 40mg b.i.d.) for 4 months. Primary end point was the reduction of the Reflux Symptoms Index (RSI), Leicester Cough Questionnaire (LCQ) and the Reflux Findings Score (RFS) by more than 50% at 4 months from baseline. Results Forty-one patients (39% female; mean age 55.9 ± 15.19 years) were enrolled, most of them with mean cough duration of more than 1 year. The primary end point was achieved in 39% of patients. Predictors of response included higher educational level (p = 0.035), hyperemia of the arytenoids and the postcricoid area (p = 0.026), and hoarseness (p p