A randomized, prospective, double blind clinical study was performed on 42 patients who underwent open heart surgery so as to compare the effects of ranitidine and sucralfate used as prophylactic agents against acute stress ulceration. Group 1 (n=22) patients were given sucralfate while group 2 (n=20) received ranitidine. Preoperative, early postoperative, first, and second day; pH of the gastric fluid was measured ant throat cultures were examined. Variables which may become a risk for florachange or infection including age, disease, diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, chronic renal failure, anemia, cross clamp time, extracorporeal circulation time, mechanical ventilation time (MVT), low cardiac output syndrome, iotropic and/or mechanical support need were compared between the groups. Statistical analysis was performed using Mann-Whitney U, Chi-square and Fishers exact test. P<0.05 was considered significant. There was no statistically significant difference between the groups related to variables mentioned above, except MVT (11.3±3 versus 15.3±3.5 hours) was longer in G2 (p<0.005). When the total number of 182 throat cultures were examined, in 10 out of 22 (45%) cases were found having significant oropharyngeal flora change cmopared to preoperative samples in G1 while in 15 out of 20 (75%) cases among G2. Abnormal colonization all with enteral microorganisms but one Streptococcus pneumoniae was more common in G2, and the difference between the groups was found statistically significant (p=0.015). Normal microbial flora may change due to several factors in patients underwent open heart surgery. This clinical study has shown that retrograde microbial translocation occurs more frequently in ranitidine-treated patients compared to sucralfate-probably related with elevation of gastric fluid pH. Based on these findings and the cost analysis which showed that ranitidine is 5 fold more expensive, and the knowledge of equal efficacy, we think taht sucralfate should be the preferred agents against stress ulceration during open heart surgery.