Introduction: Fentanyl induced cough (FIC) often follows bolus fentanyl administration in 18% up to 65% of cases. Several researches have been done to reduce such side effect. Our hypothesis is that pretreatment with intravenous dexmedetomidine-magnesium sulfate could effectively suppress fentanyl induced cough. Patients and methods: 200 patients of (ASA) I and I aged 18-60 years, weighting from 40 to 90 kg, undergoing elective surgeries, were randomized into four groups using sealed envelope system. Patients belong to (D) group received DEX 0.5 lg/kg. Patients belong to group (M) received magnesium sulfate 20 mg/kg, and those of group (D + M) received DEX 0.5 lg/kg + magnesium sulfate 20 mg/kg. The above preparations were reconstructed by saline to reach a volume of 20 ml. Patients belong to group (S) received 20 ml normal saline. Patients of each group received their cross bonding drug one minute before fentanyl bolus injection (2 lg/kg within 5 s). The primary end points were the onset time, frequency and severity of cough from time of fentanyl injection till 1 min. According to four point scale, severity of cough was graded as follows: grade 0 = no cough; grade 1 = single cough; grade 2 = more than one attack of non-sustained cough; grade 3 = repeated and sustained cough with head lift. Results: Nineteen (38%) cases had cough in group (S), 8(16%) in group (D) and 14(28%) cases in group (M). No patients in group (D + M) experienced any cough. Patients of groups (D) and (D + M) showed a significantly lower incidence of cough compared with group (S) (P < 0.05). There was no significant difference regarding the onset time or severity of cough between groups. Conclusion: Pretreatment with dexmedetomidine-magnesium sulfate could effectively suppress fentanyl induced cough following injection of 2 lg/kg fentanyl injected within 5 s.