In some patients with acute cerebral vessel occlusion, navigating mechanical thrombectomy systems is difficult due to tortuous anatomy of the aortic arch, carotid arteries, or vertebral arteries. Our purpose was to describe a multiple coaxial catheter system used for mechanical revascularization that helps navigation and manipulations in tortuous vessels. A triple or quadruple coaxial catheter system was built in 28 consecutive cases presenting with acute ischemic stroke. All cases were treated by mechanical thrombectomy with the Penumbra System. In cases of unsuccessful thrombo-aspiration, additional thrombolysis or angioplasty with stent placement was used for improving recanalization. The catheter system consisted of an outermost 8-Fr and an intermediate 6-Fr guiding catheter, containing the inner Penumbra reperfusion catheters. The largest, 4.1-Fr, reperfusion catheter was navigated over a Prowler Select Plus microcatheter. The catheter system provided access to reach the cerebral lesions and provided stability for the mechanically demanding manipulations of thromboaspiration and stent navigation in all cases. Apart from their mechanical role, the specific parts of the system could also provide access to different types of interventions, like carotid stenting through the 8-Fr guiding catheter and intracranial stenting and thrombolysis through the Prowler Select Plus microcatheter. In this series, there were no complications related to the catheter system. In conclusion, building up a triple or quadruple coaxial system proved to be safe and efficient in our experience for the mechanical thrombectomy treatment of acute ischemic stroke.