Abstract Background: General anesthesia predisposes a patient to regurgitation and aspiration of gastric substances into otherwise healthy lungs leading to fatal acid aspiration syndrome. Historically, this syndrome most commonly described as aspiration pneumonitis or Mendelson’s syndrome, was reported in 1946 in patients who aspirated while receiving general anesthesia during obstetrical procedure. Every practicing anesthesiologist thus has a key concern to this preventable devastating clinical condition which causes progressive lung damage due to the acidic solution. Objective: To assess the effect of single intravenous dose of esomeprazole sodium 40 mg and pantoprazole 40 mg administered a night before elective surgery and anesthesia in reducing intragastric pH and volume of gastric juice. Methods: This is a prospective, controlled, randomized, single blinded study conducted in 60 patients of American Society of Anesthesiologists grade I and II posted for elective surgery under general anesthesia. The patients enrolled in the study were randomly assigned to two groups having 30 patients in each. Group P received ivy pantoprazole 40 mg; Group E received iv esomeprazole 40 mg a night previous to surgery. The observer was totally blind about the groups or drugs given to the patients. On the day of surgery, after induction of anesthesia gastric juice was obtained via nasogastric tube and was checkedfor pH using pHmeter. Results: Mean pH of group P was 5.15± 0.68 which is significantly lower than group E, who received ivy esomeprazole sodium with mean pH of 6.6±0.67, (P<0.001), as shown by twotailed independent T test. Among the group P the mean gastric aspirate volume was 9.56±2.52 ml, and in group E mean gastric aspirate volume was 5.66±2.36 ml, which was statistically lower in group E as compared to group P. Conclusions: From the observations and analysis of the present study, it can be inferred that esomeprazole sodium 40 mg i.v is more effective than pantoprazole 40 mg iv to raise the gastric pH for prevention of aspiration pneumonitis.