BACKGROUND: A reflex cough is often observed after an intravenous (IV) bolus of remifentanil. Since ketamine was reported to be effective in modulating the cough reflex, this prospective, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy of pretreatment with ketamine on remifentanil-induced cough. METHODS: 320 patients undergoing general anesthesia for elective surgery were randomly allocated into two groups to receive either IV ketamine 0.1 mg/kg (ketamine group, n = 156) or 0.9% saline (saline group, n = 154) 1 min before administration of remifentanil at a target effect-site concentration of 5 ng/ml. Severity of cough was graded (mild, 1-2; moderate, 3-4; and severe, 5 or >5). RESULTS: The overall incidence of cough was significantly higher in the saline group (43/154 patients; 0.28, 95% CI 0.21, 0.36) than that in the ketamine group (18/156 patients; 0.12, 95% CI 0.07, 0.18) (P < 0.001). However, there was no significant difference in the severity and the onset time of cough between the groups. CONCLUSIONS: IV ketamine 0.1 mg/kg one minute before remifentanil was effective in suppressing remifentanil-induced cough without affecting the severity and onset time.