Gastroesophageal reflux may be responsible for atypical symptoms such as chronic cough and hoarseness. Our aim was to evaluate and treat patients with severe gastroesophageal reflux and chronic cough or hoarseness with intensive antireflux therapy. Twenty-seven patients with typical heartburn symptoms in addition to significant cough or hoarseness were treated with aggressive antireflux therapy. We recorded the response of each symptom to the antireflux therapy. Two patients were lost to follow-up. Twenty of the 25 (80%) patients showed some improvement in cough or hoarseness, nine (36%) had no atypical symptoms at follow-up. The response of heartburn to therapy was strongly predictive of successful therapy for the atypical symptoms. Cough and hoarseness improved in only two of the five patients with residual heartburn symptoms compared to 18 of 20 patients with no heartburn (P < 0.04). Only patients with no heartburn symptoms at follow-up had complete resolution of atypical symptoms. There were no important differences on ambulatory pH monitoring between partial and complete responders. Improvement in atypical reflux symptoms, such as chronic cough and hoarseness, is common with aggressive antireflux therapy. There are no findings on ambulatory esophageal pH monitoring that uniquely identify patients who are likely to respond to antireflux therapy.