Background: Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome. Methods: All patients enrolled in the German Stroke Registry (June 2015–December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge). Results: Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94–0.96]), prestroke modified Rankin Scale (0.48 [0.42–0.55]), admission-NIHSS (0.96 [0.94–0.98]), 24-hour NIHSS (0.83 [0.81–0.84]), diabetes (0.56 [0.43–0.72]), proximal middle cerebral artery occlusions (0.78 [0.62–0.97]), passes (0.88 [0.82–0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00–1.14]), successful recanalization (2.39 [1.68–3.43]), intracerebral hemorrhage (0.51 [0.35–0.73]), and recurrent strokes (0.54 [0.32–0.92]). Mediation analysis showed a 20 percentage points (95% CI‚ 17–24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI‚ 44%–66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI‚ 62%–90%) by NIHSS at hospital discharge. Conclusions: Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.