Fentanyl is commonly used during anaesthesia and can cause fentanyl-induced cough (FIC). This study investigated whether a priming dose of fentanyl reduced FIC, and determined the factors associated with increased risk of FIC. Subjects undergoing elective surgery under general anaesthesia (n = 800) were randomized into four groups: group 1 received 2 μg/kg fentanyl bolus; groups 2, 3 and 4 received a priming dose of fentanyl 0.5 μg/kg followed by 1.5 μg/kg after 1, 2 or 3 min, respectively. The incidence of FIC was 17.0%, 10.0%, 12.5% and 11.5% for groups 1, 2, 3 and 4, respectively, with no significant between-group differences in FIC incidence or severity. The mean FIC onset time was 22 s. Former smokers were 2.91 times more likely than current smokers to experience cough. A fentanyl priming dose did not reduce the incidence and severity of FIC. Former smokers were hyper-reactive to fentanyl compared with current smokers.