The objective of this study was to investigate the incidence and predictors of first-pass effect (FPE) and to compare the clinical outcomes among FPE, multiple-pass effect, and incomplete reperfusion (ICR) in acute anterior circulation large vessel occlusion. Patients from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) registry were included. FPE was defined as complete reperfusion after a single pass of the thrombectomy device without rescue treatment. MPE was defined as complete reperfusion after ≥ 2 passes of the thrombectomy device. ICR was defined as a modified Thrombolysis in Cerebral Infarction score of 2b independent of the number of passes. Multivariable analyses were used to determine predictors of FPE and to compare the following outcomes: functional independence, mortality within 90 days, intraprocedural complications, and intracranial hemorrhage (ICH) among FPE, MPE, and ICR. There were 1139 patients, of whom 307 (27.0%) achieved FPE. FPE was related to occlusion location (M1 vs internal carotid artery [ICA], adjusted OR [aOR] 1.57, 95% CI 1.15-2.15, p = 0.004; M2/anterior cerebral artery vs ICA, aOR 2.06, 95% CI 1.32-3.22, p = 0.002) and negatively associated with underlying intracranial atherosclerosis disease (ICAD) (aOR 0.33, 95% CI 0.23-0.49, p < 0.001). Patients with FPE had a higher rate of functional independence (52.7% of FPE patients vs 45.6% of MPE patients and 37.1% of ICR patients, p = 0.002; MPE vs FPE, aOR 0.69, 95% CI 0.51-0.95, p = 0.023; ICR vs FPE, aOR 0.45, 95% CI 0.31-0.66, p < 0.001), lower rate of intraprocedural complications (4.2% vs 18.1% and 21.2%, p < 0.001; MPE vs FPE, aOR 6.23, 95% CI 3.36-11.54, p < 0.001; ICR vs FPE, aOR 7.70, 95% CI 3.97-14.94, p < 0.001), and lower rate of ICH within 24 hours (18.3% vs 27.9% and 26.9%, p = 0.009; MPE vs FPE, aOR 1.97, 95% CI 1.35-2.86, p < 0.001; ICR vs FPE, aOR 2.03, 95% CI 1.30-3.16, p = 0.002) than those with MPE and ICR. FPE was achieved at a rate of 27.0% and associated with functional independence, decreased intraprocedural complications, and ICH. Non-ICA occlusion and underlying ICAD were predictors of FPE.