Nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, has been used as an anti-angina drug that causes coronary vasodilation of both epicardial and resistance vessels. We assessed the hyperaemic efficacy of nicorandil for the measurement of coronary fractional flow reserve (FFR). In this prospective, single-centre study, we enrolled 20 consecutive patients (20 lesions) with intermediate coronary artery stenosis. Hyperaemic efficacy of intracoronary bolus injection of nicorandil (2 mg) was compared with that of continuous intravenous infusion of adenosine triphosphate (ATP, 150 μg/kg/min). The intra-patient difference of FFR value between the two hyperaemic stimuli was evaluated using a non-inferiority design with the margin of 0.03. Among study patients, no serious event occurred with administration of either stimulus. A strong and linear correlation of FFR with ATP and nicorandil was observed (r (2) = 0.98, P < 0.0001). The intra-patient difference of the FFR between nicorandil and ATP was 0.003 (95 % confidence interval -0.004 to 0.011), and the probability for the non-inferiority margin of 0.03 was <0.0001. In conclusion, bolus intracoronary injection of nicorandil was non-inferior to continuous intravenous injection of ATP in achieving maximal hyperaemia. Nicorandil could be considered as an alternative option for achieving maximal coronary and myocardial hyperaemia for the assessment of FFR.