OBJECTIVE To determine the effect of upper gastrointestinal (UGI) surgery on liver function tests, a study was performed at Loghman Hakim Hospital, Tehran, Iran. METHODS In this quasi-experimental study, 60 patients undergoing UGI operations were compared to 20 patients with extra-abdominal surgery. In each case, after obtaining a thorough past medical history and physical exam, 5 ml of fasting venous blood was drawn pre-operatively on the morning of the operation, and liver function tests (LFTs), namely serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH), were measured. The three tests were repeated on the morning of days 2 and 4, post-operatively. Other intra- and post-operative parameters were also recorded. Finally, the results were analyzed in all 80 cases using the Student's t-test, Yate's corrected chi-square and Pearson's coefficient of correlation. RESULTS The operations performed in the case group were biliary tract operations (75%), surgery on the esophagus and stomach (18.3%) and liver and pancreas operations (6.7%). The control operations consisted of head and neck surgery (45%), breast and thorax operations (35%) and prostate and testes surgery (20%). The mean duration of general anesthesia in the cases and controls was 3.62 and 3.58 hours, respectively, with no statistically significant difference. The SGOT level increased 54% in the study cases on day 2, which significantly differed with the 9% increase in the controls (p<0.05). In the cases studied, SGPT increased 65% on day 2 and 50% on day 4, with a significant difference compared to the 2% decrease and 2% increase on days 2 and 4 in the controls (p<0.005 and p<0.02, respectively). LDH levels also increased 17% on day 2 in the case group with a significant difference compared to the 8% increase in controls (p<0.05). CONCLUSIONS An increase in the levels of SGOT, SGPT and LDH in the first 4 days following UGI surgery is a common problem which seems to be due to local trauma to the liver rather than the effect of other factors such as anesthetic drugs, the duration of surgery, blood transfusions, hypotension and other underlying conditions.