Objective: We examined the cardioprotective effects of propofol and ketamine with and without N-acetylcysteine (NAC). Methods: 60 rats were divided into six groups of 10 rats each. Anesthesia induction was produced with an intraperitonal injection of ketamine in Groups 1-3 and propofol in Groups 4-6. NAC (200 mg kg(-1)) was given intraperitonally during anesthesia induction in Groups 3 and 6. Groups 2, 3, 5, and 6 were subjected to 90 s of myocardial ischemia by clamping the ascending aorta, and then reperfusion was begun by unclamping the ascending aorta. After 60 min of reperfusion, blood samples were taken from the ascending aorta for biochemical analyses, and heart tissue samples were taken for biochemical and histopathological analyses. Results: Creatine kinase (CK), myocardial band of creatine kinase (CK-MB), and troponin-I (Tn-I) levels were significantly higher in the ischemia-reperfusion groups (2, 3, 5, 6) compared to the nonischemic groups (1, 4). CK, CK-MB, and Tn-I levels did not differ significantly between the ketamine groups (1-3) and the propofol groups (4-6) p >.05). Malondialdehyde levels were significantly higher in Groups 2 and 3 than in Group 1 and were significantly lower in Groups 4 and 6 than in Group 5 (p < .05). Malondialdehyde levels in the propofol groups (4-6) were significantly lower than in the ketamine groups (1-3; p < .05). Catalase levels in propofol groups were higher than ketamine groups. Superoxide dismutase levels were significantly higher in Group 6 than in Group 3 (p < .05). Conclusions: In this rat model of global cardiac ischemia, propofol with NAC attenuates myocardial injury more than ketamine (with or without NAC).