OBJECTIVE: Increasingly used Off Pump Coronary Artery Bypass Grafting (OPCABG) has significantly reduced the oxidative stress and decreased the inflammatory response associated with the use of Cardiopulmonary by Pass (CPB). However, OPCABG is associated with significant oxidative stress and its associated complications. This present study is a prospective, randomized, double blind investigating the effects of N-acetylcysteine (NAC), a potent anti-oxidant on oxidative stress in patients undergoing OPCABG. METHODS: Fifty patients undergoing elective OPCABG were randomized into two groups. Group A (n=25), the control group received 200ml of Normal saline immediately following induction, whereas Group B (n=25), the study group received 150mg/kg of NAC in 200ml of Normal saline at the corresponding time. At the end of surgery, all the patients were shifted to intensive care unit (ICU) and were extubated at the earliest possible time. Malondialdehyde (MDA), a marker of free radical injury and Glutathione (GSH) Levels were assayed from the 2 blood samples obtained (First sample immediately following induction and the second immediately after shifting to ICU). RESULTS: Demographic profile, pre-incision clinical and biochemical values were comparable in both the groups. At the end of surgery, MDA levels were significantly raised in control group (p<0.001) whereas its levels were maintained in study group (p<0.569). GSH levels were significantly decreased in control group (p<0.001) whereas its levels were significantly increased in study group (p<0.001). CONCLUSION: These results revealed that OPCABG was associated with significant oxidative response and the administration of N-Acetylcysteine attenuates this stress response by replenishing the Glutathione stores.