Background: Ventilator associated pneumonia is one of the most important nosocomial infections with often poor outcomes and heavy economic burdens on health care systems. Objectives: Several studies have been done for evaluating the effect of different types of stress related mucosal disease (SRMD) prophylaxis on nosocomial pneumonia, as among factors participating in its establishment, gastrointestinal tract is believed to play an important role especially in ventilator-associated pneumonia. Methods: In this cross-sectional study, 150 patients who were admitted to intensive care unit (ICU) and developed documented culture positive VAP, were evaluated for the study inclusion criteria. The patients with clinical pulmonary infection score (CPIS) ≥ 6 were included and some others with conditions affecting comparability excluded. The patients with Acute Physiology and chronic health evaluation II (APACHEII) scores between 10 and 24, within the first 24 hours of ICU stay, were included. Finally, 100 patients who fulfilled all criteria were evaluated for the responsible organisms and type of SRMD prophylaxis they had received. The patients included were either on intravenous pantoprazole (49 patients) or intravenous ranitidine (51 patients). The goal of this study was to evaluate the organisms, which have been isolated from the sputum of ICU patients with ventilator-associated pneumonia, according to their SRMD prophylaxis regimen. Results: There were 59 men (59) and 41 women (41) ranging from 19 to 82 years old. The mean ages were not significantly different between the two groups (P = 0.586). APACHEII score was ranging between 15 and 21 with the mean of 17.57 in pantoprazole and 16.80 in ranitidine group (P = 0.006), there was a statistical but not clinical difference. With P-value of 0.001, there was significant difference in ICU stay days. The mean mortality rates were 18.4 and 1.8 for pantoprazole and ranitidine group, respectively. The difference was statistically significant (P < 0.001). Multi-drug resistant pathogens were significantly higher in the pantoprazole group (0.001). The organisms, which have been obtained from each group were different. Acinetobacter and Pseudomonas aeruginosa were highly cultivated in the pantoprazole group, while Staphylococcus aureus and Proteus were more in patients who had received ranitidine. Conclusions: It can be suggested that each bacterium has a unique propensity to grow in specific gastric pH and other systemic changes made by various agents used for SRMD prophylaxis. More studies are needed to evaluate large number of patients receiving SRMD prophylaxis, with perspective of VAP incidence, the responsible organisms, hospital and ICU stay days, and mortality rate in order to prevent poor outcomes caused by specific organisms. © 2018, Archives of Clinical Infectious Diseases.