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Background: Multiple studies have focused on the baseline National Institutes of Health Stroke Scale (B-NIHSS) as a predictor of functional outcome after stroke. The change in NIHSS in the first 24h after stroke has been studied as a predictive variable for outcome, but the assessment of clinical improvement has been performed in various paradigms. In this study we intended to determine the accuracy of these different models. Methods: We included 369 patients in a retrospective study based on a database of 492 stroke patients. The NIHSS was calculated on admission and after 24 hours and the delta NIHSS, relative reduction (RR NIHSS) and major neurological improvement (MNI; NIHSS of 0-1 or≥8 point improvement at 24h) were calculated. The outcome at 90 days was measured by the Modified Rankin Score (mRS) and defined as good functional outcome (GFO): mRS of 0 to 2;and excellent functional outcome (EFO): mRS of 0 or 1. Independent predictors of GFO and EFO were identified by multivariate logistic regression. We performed a subgroup analysis after excluding minor stroke patients (NIHSS 0-5) since change in NIHSS at follow-up might be assessed more reliable in patients presenting with a severe deficit. Results: B-NIHSS was associated with both GFO (OR: 0.82; 95CI 0.78-0.86) and EFO (OR: 0.82; 95CI 0.77-0.86) with fair accuracy (AUC for GFO: 0.78, AUC for EFO: 0.75). Change in NIHSS after 24h was associated with GFO (OR:1.76; 95CI 1.07-2.97) and EFO (OR:2.19; 95CI 1.43-3.38) as calculated by the MNI without substantial accuracy (AUC for GFO: 0.57, AUC for EFO: 0.59).When excluding minor strokes B-NIHSS was associated with functional outcome (GFO OR:0.86; 95CI 0.79-0.93, EFO OR:0.88; 95CI 0.79-0.96) with fair to poor predictive value (AUC for GFO: 0.71, AUC for EFO: 0.66). Change in NIHSS had the most optimal accuracy (AUC for GFO: 0.67, AUC for EFO: 0.72)when determined by RR NIHSS which was associated with both GFO (OR: 6.4; 95CI 2.25-20.01) and EFO (OR:12.85; 95CI 3.69-51.55). Conclusion: B-NIHSS was associated with functional outcome with fair accuracy. Changes in NIHSS as assessed by three different definitions had less predictive value. The best predictive value of difference in NIHSS was obtained by MNI. When excluding all minor stroke this change in NIHSS had the most optimal accuracy if calculated by the RR NIHSS.