The increased production of endogenous adrenaline (ADR) with ketamine is responsible for ketamine cardiotoxicity and the short duration of anaesthesia. The aim of this study was to investigate the effect of nimesulide on ketamine cardiotoxicity, anaesthesia duration and analgesic activity. Oxidant and anti-oxidant parameters were studied in the heart tissues, while ADR, creatine kinase-MB (CK-MB) and troponin-I (TP I) levels were measured in the blood. Malondialdehide (MDA), 8-hydroxyguanine (8-OH/Gua), CK-MB, TP I, and ADR levels in the heart tissue of the ketamine group were increased and the total glutathione (tGSH) level was decreased as compared to the healthy and nimesulide groups. However, it was found that the same parameters in the ketamine-administered adrenalectomised animals were almost identical to those of the healthy animals. Nimesulide may be useful in the reduction of ketamine cardiotoxicity, providing potent analgesia and extending the duration of anaesthesia.