Introduction: Improvement in NIH stroke scale scores on 24h follow-up is considered a key prognostic element after endovascular thrombectomy (EVT). We aimed to evaluate the proportion of effect of 24h NIHSS improvement on mRS 0-2 at 90d mediated through improvement in motor and language domains. Methods: From SELECT study, EVT patients with detailed NIHSS components on presentation and 24h follow-up as well as complete mRS on discharge and 90d were selected. Motor improvement was defined as ≥2 point in cumulative arms and legs score or 0 score at 24h and language improvement was defined as ≥1 point in cumulative aphasia and dysarthria scores at 24h. Mediation analysis framework using 4-step method (Figure 1a) was used to evaluate the effect of 24h NIHSS improvement mediated through improvement in motor and language scores. Results: Of 192 eligible EVT patients, 176 demonstrated motor deficits and 187 demonstrated language deficits. 24h NIHSS improvement was significantly associated with mRS 0-2 (aOR:1.15[1.07-1.23], p<0.001) - step 1. 24h NIHSS improvement was also significantly associated with motor (aOR:1.77[1.48-2.12],p<0.001) and speech improvement (aOR:1.25[1.16-1.36],p<0.001) - step 2. In the full model, motor (aOR:3.00[1.07-8.46],p=0.037) and speech improvement (aOR:3.15[1.37-7.27],p=0.007) were significantly associated with mRS 0-2, whereas 24h NIHSS improvement was no longer a significant predictor (aOR:1.05[0.96-1.15],p=0.33) - step 3 of figure 1a. Motor improvement mediated 68% and speech improvement mediated 27% of the association of 24h NIHSS improvement with mRS 0-2 (Figure 1b) - step 4. Conclusions: Almost all (~95%) of the effect of 24h NIHSS improvement on functional independence (mRS 0-2) was mediated through specific improvement in motor and language domains, suggesting a large role of improvement in motor and language domains in achieving better functional independence. Further studies are needed to confirm the findings.