BACKGROUND: The opioid agonist fentanyl has been used at induction of anesthesia to stabilize hemodynamic parameters. But it can induce cough and in some patients, it can be hazardous. We investigated the effect of alpha2- agonist clonidine premedication on fentanyl induced cough reflex. METHODS: 83 patients (ASA class 1) were involved in this study and divided into two groups: Group 1 (no premedication group, n=43) and Group 2 (clonidine 300 microgram p .o. 1 hour prior to anesthesia, n=40). Before induction of anesthesia, in each group, fentanyl was injected within 1 second through a peripheral venous cannula in dorsum of hand and rapid fluid infusion was followed. We checked cough response, cough emerging time and it's duration. We graded the duration of cough into grade I and II (Grade I: shorter than 5 seconds, Grade II: longer than 5 seconds). RESULTS: There was no significant difference in the incidence of fentanyl induced cough reflex between Group 1 (34.9%) and Group 2 (25.6%). The incidence of Grade II is higher in Group 1 (18.3%) than in Group 2 (2.5%). CONCLUSIONS: Clonidine, as a premedication agent, couldn't reduce the incidence of fentanyl induced cough reflex. But it reduced the degree of cough response.