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Background The use of balloon guide catheter (BGC) has been associated with better reperfusion and clinical outcomes in mechanical thrombectomy (MT) for large vessel occlusion stroke. However, the impact of BGC on angiographic and clinical outcomes in patients with distal medium vessel occlusion (DMVO) strokes undergoing MT has not been extensively investigated.Methods This is a retrospective analysis of a prospectively collected database from 14 comprehensive stroke centers in the United States and Europe. Patients with anterior circulation DMVO due to middle cerebral artery (MCA) M3/M4 or anterior cerebral artery (ACA) A1/A2-3 were included. The cohort was divided into BGC and non-BGC groups. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) were used for comparison. The primary outcome was first pass effect (FPE) defined as modified treatment in cerebral infarction (mTICI) grade 2C/3 after single device pass.Results Among 199 patients who were eligible for analysis, 81 (40.7%) were female. The median age was 69 (60-81) years, and National Institutes of Health Stroke Scale score was 13 (7–18). The BGC group (n=73) had higher rates of FPE (53.4% vs 13.7%; IPTW aOR 5.63, 95%CI (2.43 to 13.10), P<0.001) compared with the non-BGC group (n=126). The BGC group had higher rates of modified Rankin Scale (mRS) 0-1 (42.9% vs 27.1%; IPTW aOR 2.78, 95% CI (1.10 to 7.07), P=0.031), mRS 0-2 (60.3% vs 41.5%; IPTW aOR 4.31, 95% CI (1.66 to 11.19), P=0.003), and lower rates of mortality at 90-days (12.7% vs 25.4%; IPTW aOR 0.32, 95% CI (0.11 to 0.98), P=0.047) compared with the non-BGC group. The rates of successful reperfusion at the end of the procedure and symptomatic intracerebral hemorrhage were comparable between both groups.Conclusion The present study suggests that the use of BGC in DMVO undergoing MT may be associated with improved angiographic and clinical outcomes with no safety concerns. Prospective studies are warranted.