Persistent left superior vena cava (PLSVC) is the most common congenital malformation of the thoracic venous system, being present in 0.3% to 0.5% of the general population. In the majority of the cases, PLSVC is asymptomatic, but in certain patients, it can manifest through several symptoms, such as arrhythmias and cyanosis, especially when it is associated with complex cardiac pathologies. The clinical significance of this venous anomaly depends on the anatomical variant of the drainage site. In this article, we will present the experience of our clinic, with patients with PLSVC that were diagnosed intraprocedurally, during cardiac pacemaker (CP) or cardioverter defibrillator (ICD) implantation, highlighting the technical difficulties that this anomaly poses for cardiac device implantation. Out of 4000 patients who were admitted to our clinic for CP or ICD implantation, we encountered six cases of PLSVC (four reported in this article and two previously published) corresponding to different anatomical types of this congenital anomaly. In all of these situations, we had to adapt our technique to the patient’s anatomy in order to avoid certain complications, the most serious being the improper placement of the right ventricle lead at the level of the coronary sinus.