The role of proton pump inhibitor in the treatment of laryngopharygneal reflux disease (LPRD) has been advocated, but there has been few reports dealing with large population based on time-related efficacy of rabeprazole. It was designed to assess the efficacy of rabeprazole and to evaluate which symptoms or findings varied significantly as medication sustained. Multiorgan, open-label cohort, prospective observational study was designed. We identified 1,142 patients with LPRD, and enrolled 455 patients, who participated fully in this survey and follow-up observation for 12 weeks. Reflux symptom index (RSI) and reflux finding score (RFS) were used to evaluate therapeutic efficacy. These parameters were evaluated at the 4th, 8th, and 12th weeks, respectively. Valid rate was used to explain improved proportion of patients after medication. The most common symptom was a globus sense in the throat. Posterior commissure hypertrophy was the most frequently encountered laryngoscopic finding. Female patients complained of heartburn and chest pain more than did male patients (P < 0.001), whereas male patients showed ventricular obliteration and erythematous changes more frequently than did female patients (P < 0.001). By RSI evaluation, scores gradually declined. Each item of the RSI improved at every visit (P < 0.001). Total RFS decreased progressively for 12 weeks and similar results were seen when every RFS item was individually examined. The proportion of patients who showed RSI and RFS falling by more than 50% after medication increased gradually as follow-up continued. This trend seemed to be significant (P < 0.001). Side effects of therapy were minimal. Despite the some constraints of an observational study, rabeprazole appeared to improve LPRD symptoms and signs. Prolonged medication at least 3 months may be beneficial to LPRD patients. Long-term medication effects require further evaluation.