Persistence of the left superior vena cava (PLSVC), observed in 0.3% of the general population as established by autopsy, is an anatomic variation particularly relevant when occurring in patients in need of a transvenous pacing. In this report, we describe a hybrid right-left cardiac resynchronization therapy defibrillator implantation approach in a patient with PLSVC. In our experience, the described approach proved feasible and safe, and may be considered an option in case of complex vein anatomy before referring for cardiac surgical implantation of a left ventricular lead.