Background Despite the use of embolic protection devices, no-reflow can still occur during saphenous vein grafts (SVGs) intervention. High-dose intracoronary adenosine infusion preconditions the myocardium, improves coronary flow, and prevents no-reflow. The role of high-dose intragraft adenosine infusion on protection of microvascular function and prevention of no-reflow has not been investigated Objectives We investigated the cardioprotective effect of high-dose intragraft adenosine infusion, compared with placebo, on microvascular function and prevention of no-reflow during SVGs intervention. Methods: We randomized 22 patients with SVGs stenoses to receive either a 10-min intragraft adenosine infusion (200 μg/min; total dose-=-2,000 μg) or normal saline prior to stenting. Average peak velocity (APV), coronary flow velocity reserve (CVR), thrombolysis in myocardial infarction (TIMI) frame count (TFC), TIMI myocardial perfusion grade (TMPG), and the rate of no-reflow were compared between the two groups before adenosine or saline infusions and after stenting Results After stenting, hyperemic APV, CVR, and TMPG were significantly higher in the adenosine-treated group than in the control group (60-±-18 vs. 35-±-10 cm/sec; 2.6-±-0.54 vs. 1.8-±-0.47; and 2.8-±-0.90 vs. 2.1-±-0.80, respectively; P-<-0.05. TFC was significantly lower in the adenosine-treated group than in the control group (14-±-3.0 vs. 26-±-13; P-<-0.05). In the control group, four patients (36%) developed no-reflow compared to none in the adenosine-treated patient; P-<-0.05 Conclusions This study provides the first evidence that high-dose intragraft adenosine infusion compared with placebo protects microvascular function and prevents no-reflow during SVGs intervention. © 2013 Wiley Periodicals, Inc.