There is equivocal evidence examining cognitive improvement in response to lidocaine during cardiac surgery; however, no study has examined its effect on postoperative neuropsychological-cognitive decline after supratentorial tumor surgery. Methods: Ninety-four patients scheduled for supratentorial craniotomy were enrolled. Patients received either a dose of lidocaine (2%) via an intravenous bolus (1.5 mu g/kg) after induction followed by an infusion at a rate of 2 mu g/kg/h until the end of surgery (Lidocaine group) or the same volume of normal saline. The neuropsychological-cognitive decline was evaluated using the following tests: the Mini-Mental State Examination, the Information-Memory-Concentration test, the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety. The cerebral oxygen extraction ratio and the difference in lactic acid levels between the bulb of the jugular vein and a peripheral artery were measured. Results: Eighty patients completed the neuropsychological tests, with 40 patients in each group. The incidence of postoperative decline at up to 6 months in the Lidocaine group was not significantly different than that in the Normal saline group. When the 2 cognitive tests were examined independent of the other tests, there was no difference between groups at 6 months. The cerebral oxygen extraction ratio was significantly lower in the Lidocaine group after surgery (P<0.05), and the arteriovenous difference of lactic acid was lower in the Lidocaine group (P<0.05). Conclusions: Intraoperative infusion of lidocaine does not significantly decrease the incidence of postoperative neuro-psychological-cognitive decline in patients 6 months after supratentorial tumor surgery.