Introduction: Recent trials have demonstrated the superior efficacy of mechanical thrombectomy over other medical treatments for acute ischemic stroke; however, not every large vessel occlusion (LVO) can be recanalized using a single thrombectomy device. Rescue devices were proved to increase the reperfusion rate, but the efficacy is unclear.Objective: In this retrospective study, we evaluated the efficacy of rescue therapy in different locations of LVO.Methods: We analyzed the outcomes of mechanical thrombectomy from a prospective registry of consecutive 82 patients in Taipei Medical University Hospital. The reperfusion rate and the functional outcome were compared in patients who received first-line therapy only and patients who need rescue therapy.Results: An 84.1% reperfusion rate was achieved in our cohort. We applied first-line stent retriever (SR) treatment in 6 patients, among which 4 (66.6%) achieved successful reperfusion. We applied a direct-aspiration first-pass technique (ADAPT) as the first-line treatment in 76 patients, among which 46 (60.5%) achieved successful reperfusion. Successful reperfusion could not be achieved in 30 cases (39.5%); therefore, we applied a second-line rescue SR for 28 patients, and reperfusion was established in 18 (64.3%) of them. These results revealed that the LVO in anterior circulation has a higher chance to respond to SR rescue therapy than posterior circulation lesions (68 vs. 33.3%, P < 0.001). Patients who received only first-line therapy exhibited significantly better functional outcomes than those who were also treated with rescue SR therapy (41.2 vs. 16.7%, P = 0.001). In addition, patients with LVO in the anterior circulation were found to have a higher probability of achieving functional independence than patients with posterior circulation lesions (10.7 vs. 0.0%, P < 0.001). The adjusted multivariate analysis revealed that successful reperfusion and treatment type (first-line or rescue therapy) were significantly related to a modified Rankin Scale (mRS) score at 90 days.Conclusion: This study reveals that rescue SR therapy improves the reperfusion rate. Patients who require rescue SR therapy have a lower likelihood of functional independence. LVO in the anterior circulation responds better to rescue SR therapy and results in better functional outcomes than posterior circulation lesions.