Background: Globus pharyngeus is a multifactorial disorder with a mostly unidentified cause, which is defined as a non-painful sensation of a lump, foreign body, or tightness in the throat. Over 4% of all ENT clinic patients complain of globus sensation, which is quite common among the general population. Since the major cause of the globus is found to be GERD (Gastroesophageal reflux disease), the most practical therapeutic management of the globus would be empirical proton pump inhibitors (PPI) as a first attempt. Reflux symptom index (RSI) and reflux finding score (RFS) were initially used to document the clinical severity of laryngopharyngeal reflux (LPR) and to assess treatment efficacy. The RFS and RSI scores were used in this study to investigate the response rate and clinical predictors of symptom response to PPI treatment in patients with globus pharyngeus. Materials and methods: This Prospective interventional study was performed in the department of E.N.T at tertiary care teaching hospital in rural karnataka over 18 months. A sample of 100 globus pharyngeus patients was selected and evaluated using RSI and RFS on enrollment. They were treated with a twice-daily dose of esomeprazole 40mg for 2 months and RSI & RFS were readministered. Pre and post-treatment scores were compared and changes in the severity of globus pharyngeus correlated with the change in scores. Results: Before the treatment, 65% of the patients had RSI >13 and 66 % of the patients had RFS ˃7, after the treatment RSI was significantly reduced, with patients having RSI >13 being 12 % and RFS score >7 seen in only 1% of the patients. Further evaluation showed that a statistically significant reduction was seen in RSI with a p-value of 0.017 and RFS scores with a p-value of 0.0001. Evaluation of mean RSI and RFS scores between responders and non-responders did not show any significant difference pre and post-treatment symptoms concerning globus pharyngeus. Conclusion: The empirical treatment of all globus pharyngeus patients with esomeprazole is not effective. Globus pharyngeus was relieved with esomeprazole in patients whose symptoms were due to laryngopharyngeal reflux. Esomeprazole was not universally helpful in globus patients with high RSI and RFS scores. Also, RSI and RFS cannot be used as predictors for PPI response in globus pharyngeus patients according to our study.