The no-reflow phenomenon is an often seen complication in patients presenting with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This event is associated with poor prognosis and poses a therapeutic challenge. This retrospective study cohort was composed of 30 patients who presented with ACS between September 2007 and April 2009, and developed no-reflow during subsequent PCI. The primary end-point was defined as normal Thrombolysis In Myocardial Infarction (TIMI) 3 flow with myocardial blush grade (MBG) >or=2 or an increase in TIMI flow by >or=2 grades with a MBG >or=2 after intracoronary drug infusion via the ClearWay (CW) RX perfusion catheter. The population presented with a relatively high prevalence of cardiovascular risk factors. ST-elevation myocardial infarction was the most common presentation (60.0%), while 20% of the patients presented with cardiogenic shock. After intracoronary infusion of nicardipine or nitroprusside using the CW catheter, TIMI flow improved from the baseline in 19 cases (63.3%, P < 0.001), and 16 patients (53.3%, P < 0.001) achieved normal coronary flow at the end of the procedure. The rate of in-hospital death was 6.7% (2 cases). No clinical differences were noted between those patients who successfully achieved normal coronary flow and those with persistent no-reflow. The infusion of intracoronary drugs using the novel perfusion CW RX catheter seems to be safe and could help to improve myocardial perfusion in a selected group of patients presenting with ACS who developed no-reflow during PCI.