Persistent sciatic artery (PSA) is a rare vascular anomaly classified into five types according to the Pillet and Gauffre classification system. Although PSA may be detected as an incidental finding, symptomatic cases account for approximately 80% of all cases and have variable clinical presentations. Due to the frequent ischemic and aneurysmal complications, PSAs can lead to limb-threatening conditions requiring prompt identification and adequate treatment management. In this paper, we present a series of four cases of PSA with extremely different anatomical characteristics, patients’ ages, medical histories and clinical presentations. All cases were diagnosed in our institution and managed after multidisciplinary discussions involving vascular surgeons and interventional radiologists. The series included three women and one man. In two cases, one of which included gluteal and back pain, pulsatile masses were found. Two patients had lower-limb chronic ischemia, one with rest pain and one with IIb claudication. Whereas selective angiography was performed only in endovascular approaches, computed tomography angiography (CTA) was performed on all patients as the decisive diagnostic modality. In our series, treatment strategies were selected on the basis of clinical and anatomical factors, and after the evaluation of the potential risks and benefits of each technique. Treatment was medical in two cases, endovascular in one case and hybrid in one case.