The aim of this study was to evaluate the effectiveness of lidocaine, propofol and ephedrine in suppressing fentanyl-induced cough. One hundred and eighteen patients were randomly assigned into four groups and the following medications were given intravenously: patients in Group I (n = 31) received normal saline 2 mL, Group II (n = 29) received lidocaine 2 mg.kg(-1), Group III (n = 30) received propofol 0.6 mg.kg(-1) and Group IV (n = 28) received ephedrine 5 mg. At one minute after the study medication, fentanyl 2.5 microg.kg(-1) was given intravenously within two seconds. The occurrence of cough and vital sign profiles were recorded within two minutes after fentanyl bolus by an anesthesiologist blinded to study design. Sixty-five percent of patients in the placebo group had cough, whereas the frequency was significantly decreased in Groups II (14%) and IV (21%). Although a numerically lower frequency of cough was noted in Group III (37%), it was not statistically different from that of the placebo group. SpO(2) decreased significantly in patients of Group III compared to placebo; one patient experienced hypoxemia necessitating mask ventilation. Patients in Group III showed a decrease in heart rate and systolic blood pressure (2 beats.min(-1) and 8 mmHg vs baseline). Patients in Group IV showed an increase in both measurements (5 beats.min(-1) and 8 mmHg vs baseline). No truncal rigidity was observed throughout the study. Intravenous lidocaine 2 mg.kg(-1) or ephedrine 5 mg, but not propofol 0.6 mg.kg(-1), was effective in preventing fentanyl-induced cough. The results provide a convenient method to decrease fentanyl-induced cough.