Objective To determine the effect-site concentration (Ce) of remifentanil target-controlled infusion required for a smooth inhalational induction without airway irritation using desflurane in a stepwise incremental manner for 50% of patients (EC50) and 95% of patients (EC95). Methods Patients with an American Society of Anesthesiologists physical status I and II, aged 19-60 years undergoing elective surgery were enrolled in this study. When target Ce of remifentanil was reached, desflurane was inhaled at 4 vol% initially and then it was increased to 8 and 12 vol% at intervals of 30 s. Smooth induction was regarded as an absence of airway irritation signs and excitatory movements. The EC50 and EC95 values for remifentanil were determined using a modified Dixon's up-and-down method as well as an isotonic regression method with a bootstrapping approach. Results The EC50 and EC95 of remifentanil for smooth induction during inhalation of desflurane were 3.40 ng/ml (95% confidence interval [CI] 2.42, 4.38 ng/ml) and 4.31 ng/ml (95% CI 2.15, 5.98 ng/ml), respectively. Conclusion Prior administration of remifentanil could provide smooth inhalational induction with desflurane in a stepwise increment.