Purpose: To compare outcomes after endovascular treatment (EVT) for acute ischemic stroke with and without the use of a balloon guide catheter (BGC) in clinical practice. Materials and Methods: Data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry were used, in which all patients who underwent EVT for anterior-circulation stroke in The Netherlands between 2014 and 2016 were enrolled. Primary outcome was modified Rankin scale (mRS) score at 90 days. Secondary outcomes included reperfusion grade (extended Thrombolysis In Cerebral Infarction [eTICI] score) and National Institutes of Health Stroke Scale (NIHSS) score 24–48 hours after intervention. The association between the use of a BGC and outcomes was estimated with logistic regression adjusted for age, sex, prestroke mRS score, NIHSS score, collateral grade, and time from onset to EVT. Results: A total of 887 patients were included. Thrombectomy was performed with the use of a BGC in 528 patients (60%) and without in 359 patients (40%). There was no significant association between use of a BGC and a shift on the mRS toward better outcome (adjusted common odds ratio, 1.17; 95% confidence interval [CI], 0.91–1.52). Use of a BGC was associated with higher eTICI score (adjusted common OR, 1.33; 95% CI, 1.04–1.70) and improvement of ≥ 4 points on the NIHSS (adjusted OR, 1.40; 95% CI, 1.04–1.88). Conclusions: In clinical practice, use of a BGC was associated with higher reperfusion grade and early improvement of neurologic deficits, but had no positive effect on long-term functional outcome.