Aims Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO) intermittently increases the pressure in the cardiac venous outflow tract using a balloon-tipped catheter introduced percutaneously into the coronary sinus. It aims to improve microvascular perfusion in STEMI patients during PCI, thus improving infarct healing. Its successful administration was associated with an improvement in myocardial recovery four months after primary-PCI as compared to control. However, it has never been used in other set tings or for a prolonged period. The aim of this study was to report on the feasibility and efficacy of prolonged PICSO to treat refractory LV dysfunction and ischemia. Methods and results Two patients with refractory LV dysfunction and ongoing ischemia with patent epicardial coronary artery and suspected underlying microvascular dysfunction were treated with prolonged off-label PICSO utilization. A medium of 23,990 mmHg PICSO quantity (a marker of PICSO therapy performance) was achieved: it was almost fifty times the PICSO quantity previously reported in in short-term PICSO utilization. After PICSO placement, both patients showed significant improvement of myocardial ischemia and recovery of LV systolic function. Conclusion Prolonged PICSO utilization was feasible and effective in two patients. These cases highlight a novel application of PICSO technology: redistribution of venous blood and improvement in microvascular perfusion that might be a new target in cases of refractory LV dysfunction and ongoing ischemia in the setting of patent epicardial coronary arteries. © 2017 Elsevier B.V.