Laryngopharyngeal reflux (LPR) is a variant of gastroesophageal reflux disease (GERD) in which the stomach contents go up into the pharynx and then down into the larynx. LPR causes a wide spectrum of manifestations mainly related to the upper and the lower respiratory system such as laryngitis, asthma, chronic obstructive pulmonary disease, cough, hoarseness, postnasal drip disease, sinusitis, otitis media, recurrent pneumonia, laryngeal cancer and etc. The object of this study was to examine the effect of N-acetyl Cysteine (NAC) with and without Omeprazole on laryngitis and LPR. Ninety patients with laryngitis or its symptoms were referred and randomly assigned into three groups. The first group was treated by Omeprazole and NAC. The second group was treated by Omeprazole and placebo and the last group was treated by NAC and placebo. Duration of treatment was 3 months and all patients were evaluated at the beginning of study, one month and three month after treatment of sign and symptoms, based on reflux symptom index (RSI) and reflex finding score (RFS). Based on the results of this study, despite therapeutic efficacy of all treatment protocols, the RSI before and after 3 months treatment had significant difference in (NAS+ Omeprazole) and (Omeprazole+ placebo) group (P<0.001 in the first group, P<0.001 in the second group and P=0.35 in the third group). Whereas RFS before and after 3 month treatment had significant difference in all groups. (P<0.001 in each group in comparison with itself) but this results had not significant difference after 1 month treatment. Our results showed that the combination therapy with Omeprazole and NAC treatment had the most effect on both subjective and objective questionnaire at least after 3 months treatment. Based on the results of the present study, it seems that the use objective tools are more accurate than subjective tools in evaluation of therapeutic effects in patients with GERD-related laryngitis.