Background and Purpose <p>Endovascular thrombectomy is now the standard of care for large vessel occlusion acute ischemic stroke. However, acute stroke due to medium-vessel occlusions often result in unfavorable outcomes, and guidelines for thrombectomy are lacking. Moreover, nearly all clinical data and thrombectomy trials are based on biplane angiography systems. This study aims to compare the safety and efficacy of stroke thrombectomy procedures performed on single-plane versus biplane angiography systems in patients presenting with medium-vessel occlusions of the middle cerebral artery.</p> Materials and Methods <p>This retrospective study included consecutive patients with acute ischemic stroke due to primary middle cerebral artery medium-vessel occlusions treated with thrombectomy between 7/1/2020 and 8/1/2022 at a single high-volume practice. Patients were dichotomized into those treated on single plane and biplane systems. Demographic, procedural, clinical and follow-up characteristics were compared.</p> Results <p>Among the 149 patients included, 44 underwent thrombectomy on single-plane systems, and 93 on biplane systems. No significant differences were detected in rates of good functional outcomes (mRS &lt; 2; SP 54% vs BP 42%, <i>p</i> = 0.19), successful recanalization (TICI ≥ 2B; SP 91% vs BP 86%, <i>p</i> = 0.77), intra-procedural vascular injury (SP 0% vs BP 3%; <i>p</i> = 0.56), or time from groin puncture to reperfusion (SP 25 min vs BP 27 min; <i>p</i> = 0.97). No significant differences were detected in peri-procedural complications, or symptomatic intracerebral hemorrhage.</p> Conclusion <p>Thrombectomy for middle cerebral artery medium-vessel occlusions performed on single-plane angiography systems is as safe and efficacious as biplane procedures. Our results may have implications for increasing access to care, especially in regions with limited resources.</p>