Abstract Background: Linezolid (LZD) is antibiotic belonging to Oxazolidinones group. It acts by protein synthesis inhibition and has clinical utility in the treatment of infections caused by resistant aerobic Gram-positive bacteria (as methicillin-resistant S. aureus (MRSA), Vancomycin Resistant Enterococci (VRE), and mycobacterial infections). Aim of Study: To evaluate the incidence of linezolid induced lactic acidosis in post GIT-operative patients. Patients and Methods: After ethical committee approval, 150 patients admitted to the intensive care unit (ICU) after gastrointestinal tract surgery were enrolled in this retrospective cohort study, Patients were divided into two equal groups: those who used LZD and those who used Vancomycin (VAN), to examine the incidence of lactic acidosis after administration of either LZD or VAN. Patients with other risk factors for lactic acidosis were excluded from the study. Demographic data, admission diagnosis and the result of laboratory exam-inations were recorded. The duration of antibiotic use and the use of other antibiotics were recorded from patient's medical chart. Results: The incidence of lactic acidosis was statistically significance higher in patients on LZD therapy than in those on VAN therapy (13.3% vs. 1.3%, respectively, p=0.005). The mortality rate after antibiotic administration was higher (but doesn't reach statistical significance) in patients on LZD therapy compared to those on VAN therapy (25.3% vs. 17.3%, respectively, p=0.232). In binomial logistic regression, patients on LZD therapy were statistically significance more likely to have lactic acidosis than patients on VAN therapy by approx-imately 11 times (crude OR=11.385; 95% CI=1.419-91.352; p=0.022), while age, gender, presence of comorbidity, duration, and mean fluid balance after drug intake were not statistically significance associated with a change in the probability of developing lactic acidosis. However, when these factors were entered together in the regression analysis, increase in mean fluid balance was statistically significance associated with reduced likelihood of developing lactic acidosis (adjusted OR=0.998, 95% C.I.= 0.996-1.000, p=0.047). Conclusion: LZD was not associated with significant higher incidence of lactic acidosis in comparison to Vanco-mycin in post GIT operative patients.