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Background First-pass effect (FPE), defined as achieving successful reperfusion with a single thrombectomy pass and no additional intervention, has been proposed as a procedural quality metric in endovascular thrombectomy (EVT). However, the consistency of its clinical benefit across angiographic recanalization thresholds and patient subgroups remains uncertain.Objective To evaluate the association between FPE (and non-FPE) and review clinical outcomes across multiple reperfusion thresholds as well as assess effect modification across pre-specified clinical and procedural subgroups.Methods MEDLINE, EMBASE, and Scopus were searched from inception through January 31, 2026, with supplemental backward and forward citation searching and review of ClinicalTrials.gov. Eligible studies compared outcomes between FPE and non-FPE among patients achieving successful reperfusion. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 90 days. Secondary outcomes were 90-day mortality and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analyses were performed to estimate pooled odds ratios (ORs) at modified Thrombolysis in Cerebral Infarction (TICI) ≥2b, ≥2c, and TICI 3 thresholds. Pre-specified subgroup analyses examined effect modification across 12 variables. The study was registered with PROSPERO (CRD420261297405).Results Twenty-six studies including 12,601 patients were analyzed at the TICI ≥2b threshold. Compared with non-FPE, FPE was associated with higher odds of functional independence (OR 1.88, 95% CI 1.63-2.17; I 2 = 62.0%), lower mortality (OR 0.59, 95% CI 0.51-0.70; I2 = 23.6%), and lower sICH (OR 0.57, 95% CI 0.46-0.71; I2 = 0%). Associations persisted at more stringent reperfusion thresholds, with progressively larger effect sizes for functional independence (TICI ≥2c: OR 1.85; TICI 3: OR 2.87, 95% CI 1.05-7.89). Significant effect modification was observed by vascular territory (posterior > anterior; interaction P < 0.001), diabetes prevalence (interaction P = 0.007), and sex distribution (interaction P = 0.020), with male and female-predominant cohorts showing a larger effect (OR 2.50 vs OR 3.30) than sex-balanced cohorts (OR 1.69).Conclusions FPE is consistently associated with improved functional outcomes, reduced mortality, and fewer hemorrhagic complications across angiographic reperfusion thresholds. The graded increase in benefit with more complete first-pass reperfusion and the amplified effect in posterior circulation stroke and diabetic populations support FPE, particularly first-pass complete reperfusion as a clinically meaningful quality benchmark and potentially modifiable determinant of outcome after EVT.Disclosures A. Mahadevan: None. P. Pekyi-Boateng: None. S. Nguyen: None. A. Shoskes: None. J. Charles: None. J. Majersik: None. K. Budohoski: None. R. Grandhi: None.