Background: The incidence of improper use of PPIs varies from 40-70% in various studies. Initiation and the continuous use of these drugs without correct indications will result in significant cost to the patient. The present study was planned with the aim of finding out the rational use of PPIs in the in patients of a rural tertiary care hospital. Objectives: To assess indications of use of PPIs along with their dose, frequency, rationality of treatment, safety and efficacy. Methods: Prospective observational drug-utilization study of PPIs was conducted for two months in the inpatients of General Medicine and General Surgery wards. The sample size of study was (n=100). The case sheets of the patients were reviewed for PPIs prescription and relevant data was taken. A five point Likert scale with validated Reflux Disease Diagnostic Questionnaire (RDQ) having 12 items was used for evaluating symptoms score for assessing efficacy of PPIs. Results: A total of 46.72% inpatients were on proton pump inhibitors, in surgery(47.52% ) and medicine wards (46.01%). The indications for PPIs therapy were acute gastritis (4%) , Gastro Esophageal reflux disease (5%) , Duodenal ulcer(1%) , co-administration with Non Steroidal Anti- Inflammatory Drugs(32%). PPIs were prescribed irrationally in 58 % of patients without any valid indication. The incidence of polypharmacy was high, average number of drugs per prescription was 4.93. Antimicrobials were the most common drugs used in (71%). CONCLUSION: Proton pump inhibitors should be used more judiciously and awareness should be created among the clinicians in the hospital so that appropriate prescription of PPIs will improve the patient care at low cost.