Abstract Background No-reflow is a complication of percutaneous coronary interventions (PCI), which occurs in 0.6–5% of elective PCIs, but it may be observed in up to 50% of primary PCI cases, involving the treatment of thrombus-containing lesions. An optimal standard treatment of no-reflow (NR) has not yet been established. Intracoronary (IC) vasodilators are being administered for the treatment of NR via the guiding catheter, but sometimes distal flow restoration is not satisfactory especially in patients with TIMI 0 flow. Purpose To investigate the efficacy and safety of local IC drug delivery in the distal coronary bed via a microcatheter as a treatment option of NR phenomenon during PCI. Methods A retrospective analysis of 4606 PCI procedures done in our institution was conducted, to identify patients who suffered from NR during PCI (TIMI 0-I flow in the absence of mechanical obstruction). In patients with NR, local IC infusion of vasodilators (Nitroprusside 50–200 mcg, Adenosine 30–40 mcg) was infused, via a microcatheter or thrombus-aspiration catheter, distal to the angioplasty site. Repeated injections were done with both drugs at the operator's discretion, until best flow was achieved, but without exceeding the maximum recommended dose. If the patient was hypotensive and, thus, the administration of IC vasodilators for treating slow flow/NR was impeded, 100–200 mcg IV phenylephrine were administered, to increase blood pressure. Afterwards, IC vasodilators were infused. Results In 4606 conducted PCIs, 83 patients suffered from NR (1.8%). The age of patients with NR was 65.17±11.69 years. As for the sex, there were 10 female (12.1%) and 73 male (87.9%) patients. The mode of presentation was: 1) STEMI in 28 patients (33.7%), 2) NSTEMI-Unstable Angina in 21 patients (25.3%) and 3) stable angina in 34 patients (41%). NR was observed in 57 patients (68.7%) at post-stenting and in 26 patients (31,3%) at post-dilation. The affected vessel was LAD in 35 patients (42.2%), LCx artery in 16 patients (19.3%), RCA in 28 patients (33.7%) and SVG in 4 patients (4.8%). The IC-infused drug was adenosine in 21 patients and nitroprusside in 62 patients. The total number of infusions was 4.05±1.88. TIMI III flow was achieved in 90.3% of patients and MBG II/III was achieved in 89.1%. The combination of TIMI III flow with MBG II/III was achieved in 87.9% of the patients. In the subgroup of patients with STEMI, the combination of TIMI III flow with MBG II/III was achieved in 85,7% of the patients. As for the complications, a transient systolic pressure drop below 90 mmHg occurred in 4 patients, while there was one death, due to cardiogenic shock complicating acute anterior MI. Conclusion Local IC delivery of vasodilator drugs in the distal coronary bed via microcatheter during PCI is a safe and effective treatment of NR phenomenon, and it can enhance the myocardial perfusion, in addition to reducing infarct's size. Also, it may improve the post-PCI prognosis. Funding Acknowledgement Type of funding sources: None.