Background and Purpose: We aim to evaluate if good collateral flow (CF) modifies endovascular therapy (EVT) efficacy on large-vessel stroke. To do that, we used final degree of reperfusion and number of device-passes performed, factors previously associated with better functional outcome, as main outcome measures. Methods: Single-center retrospective study including consecutive stroke patients receiving EVT for anterior circulation large-vessel stroke. CF degree was assessed on CT angiography before EVT using a previously validated 4-grade score. Final degree of reperfusion, using modified Thrombolysis in Cerebral Ischemia (mTICI), and number of device-passes performed were prospectively collected. Multivariable analysis was performed to evaluate the influence of collateral flow degree on final degree of reperfusion and number of device-passes performed. Results: Six hundred twenty-six patients were included in the study; 369 patients (59%) presented good collateral flow on CT angiography. Five hundred twenty-two patients (84%) achieved successful reperfusion (mTICI 2B-3) after EVT, 304 (48%) of them with a final mTICI 2C-3. Median number of device-passes was 2 (interquartile range, 1–3). Good CF was independently associated with better final degree of reperfusion (shift analysis for mTICI0-2A/2B/2C-3%, poor CF 19/38/43 versus good CF 15/32/53, adjusted odds ratio, 1.51 [95% CI, 1.08–2.11]). Poor CF was independently associated with higher number of device-passes performed to achieve successful reperfusion (mTICI2B-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.59, [95% CI, 1.09–2.31]) and complete reperfusion (mTICI2C-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.70 [95% CI, 1.04–2.90]). Conclusions: Patients with good CF treated with EVT experience higher rates of successful reperfusion with lower number of device-passes. CF may facilitate thrombus retrieval and prevent distal embolization of clot fragments, improving device-passes efficacy.