While several MRI parameters are used to assess tissue perfusion during hyperacute stroke, it is unclear which is optimal for measuring clinically relevant reperfusion. We directly compared mean transit time (MTT) prolongation (MTTp), time-to-peak (TTP), and time-to-maximum (Tmax) to determine which best predicted neurological improvement and tissue salvage following early reperfusion. Acute ischemic stroke patients underwent three MRIs: <4.5 h (tp1), at 6 h (tp2), and at 1 month after onset. Perfusion deficits at tp1 and tp2 were defined by MTTp, TTP, or Tmax beyond four commonly used thresholds. Percent reperfusion (%Reperf) was calculated for each parameter and threshold. Regression analysis was used to fit %Reperf for each parameter and threshold as a predictor of neurological improvement [defined as admission National Institutes of Health Stroke Scale (NIHSS)-1 month NIHSS (∆NIHSS)] after adjusting for baseline clinical variables. Volume of reperfusion, for each parameter and threshold, was correlated with tissue salvage, defined as tp1 perfusion deficit volume-final infarct volume. Fifty patients were scanned at 2.7 and 6.2 h after stroke onset. %Reperf predicted ∆NIHSS for all MTTp thresholds, for Tmax >6 s and >8 s, but for no TTP thresholds. Tissue salvage significantly correlated with reperfusion for all MTTp thresholds and with Tmax >6 s, while there was no correlation with any TTP threshold. Among all parameters, reperfusion defined by MTTp was most strongly associated with ∆NIHSS (MTTp >3 s, P = 0.0002) and tissue salvage (MTTp >3 s and 4 s, P < 0.0001). MTT-defined reperfusion was the best predictor of neurological improvement and tissue salvage in hyperacute ischemic stroke.