Objective To observe the effects of nebulized inhalation of ketamine combined with intravenous dexmedetomidine on fentanyl-induced cough and cardiovascular responses during tracheal intubation. Methods A total of 200 ASA I-II patients undergoing elective surgery were randomly divided into four groups with 50 cases in each group. Patients in each group received different therapies: inhaled ketamine (0.25mg.kg-1 diluted to 4ml with normal saline) via compressed nebulizer in ketamine group, dexmedetomidine 0.4µg.kg-1 was intravenous infused within 10min in dexmedetomidine group, nebulized inhalation of ketamine 0.25mg.kg-1 combined with intravenous dexmedetomidine 0.4µg.kg-1 in combination group, equal volume of normal saline was given instead of ketamine and dexmedetomidine in control group. Five minutes after above mentioned premedication, all patients were received fentanyl 3µg.kg-1 IV within 5 seconds. After intravenous injection of fentanyl bolus, the frequency and intensity of coughing were observed. Systolic blood pressure(SBP), diastolic blood pressure (DBP), heart rates (HR) were recorded before general anesthesia (T0) , 5 min after premedication (T1), before tracheal intubation (T2), immediately after intubation (T3), 1 min after intubation (T4), 3 min after intubation(T5). Results The rate of cough was significantly lower in ketamine group, dexmedetomidine group and combination group than that in control group (P0.05), the rate of cough were obviously lower in combination group than those of in ketamine group and dexmedetomidine group (P0.05). Compared with control group or ketamine group, SBP, DBP, HR in dexmedetomidine group and compound group at T3-T5 were decreased significantly (P0.05). Conclusion Nebulized inhalation of ketamine or intravenous infusion of dexmedetomidine before general anesthesia can effectively reduce fentanyl-induced coughing, and ketamine 0.25mg.kg-1 nebulized inhalation combined with dexmedetomidine 0.4µg.kg-1 intravenous infusion can further suppress fentanyl-induced cough.