Background: Early neurological recovery (ENR) is an attractive surrogate marker for long-term functional outcome of endovascularly-treated stroke patients. However, the optimal definition of 24-hour ENR that best predicts 90-day functional independence (modified Rankin Scale, mRS, 0-2) has not been established. We sought to determine ENR measure that best predicts 90-day mRS 0-2. Methods: The prospective BEST cohort study includes consecutive adult patients treated with endovascular therapy at 12 comprehensive stroke centers. In this post-hoc analysis, we measured the ability of various thresholds of both 24-hour NIHSS and αNIHSS (baseline minus 24-hour) to predict 90-day mRS 0-2 using Youden’s index. The strength of the associations were assessed using logistic regression adjusted for age, glucose, hypertension, ASPECT score, time to recanalization, recanalization status, and thrombolytic treatment. Results: Of 485 patients in the BEST cohort, 447 with 90-day follow-up were included in this study (228 females, mean age 68.05 ±15 years). The optimal Youden’s Index was achieved at 24 hour NIHSS of ≤7 (sensitivity 80.1%, specificity 80.4%, area under the curve [AUC] 0.855 [0.819-0.887], p<0.001; Figure). The optimal for αNIHSS cut point was ≥4 points (sensitivity 79%, specificity 58.5%, AUC 0.73 [0.685-0.77], p<0.001; Figure), which performed less well at outcome prediction than 24 hour NIHSS (difference between the AUCs 0.126, p<0.001; Figure). Strength of association between other common early clinical endpoints and outcome in this cohort are listed in the Table. Conclusions: A 24-hour NIHSS ≤7 was the optimal measure to predict functional independence at 90 days in our multicenter, prospective cohort. Among αNIHSS thresholds, ≥4 points was optimal but performed less well. These findings should be validated in independent endovascular cohorts to establish a standard short-term outcome measure for both clinical and research scenarios.