Background: Maximal hyperemia is prerequisite for the accurate measurement of fractional flow reserve (FFR). Although continuous infusion of adenosine by femoral vein is considered to be the gold-standard way of hyperemia, this requires additional invasive procedure for femoral vein access and is difficult to use during trans-radial coronary catheterization. We performed this prospective study to evaluate the feasibility and efficacy of peripheral intravenous (IV) infusion of adenosine for FFR measurement. Methods: Seventy-one patients with intermediate coronary artery stenosis were prospectively enrolled. FFR was measured using a 0.014 inch coronary pressure wire. Hyperemic efficacy of adenosine was compared among intracoronary (IC) bolus injection, continuous IV infusion (140關g/min/kg) via the femoral and via the forearm vein. In 20 patients, hyperemic mean transit time and index of microcirculatory resistance (IMR) were also measured. Results: As compared with femoral vein infusion (FFR: 0.80짹0.10), hyperemic efficacy of forearm vein infusion of adenosine (FFR: 0.80짹0.11) was not inferior (p for non-inferiority=0.01). The number of functionally significant stenosis (FFR<0.75) was also not different between the 2 methods (femoral vein vs. forearm vein; 17 (25.0%) vs. 17 (25.0%), p=1.0). The time to maximal hyperemia was longer with forearm vein infusion than with femoral vein infusion (53.7짹22.8 vs. 38.7짹17.9 seconds, p<0.01). Both hyperemic mean transit time and IMR were not different between the 2 routes of adenosine infusion. Additional bolus injection of adenosine during IV infusion did not improve the hyperemic efficacy but increased the risk of AV block. Conclusions: This study suggests that continuous IV infusion of adenosine via the forearm vein is a convenient and effective way to induce steady-state hyperemia for invasive physiologic measurements.