Background: Optimal level blood pressure (BP) targets in acute stroke remain elusive. Tailored hemodynamic management after endovascular thrombectomy (EVT) may reduce the risk of reperfusion injury and promote penumbral recovery. Our study aimed to evaluate the relationship between personalized autoregulation-based BP targets, secondary brain injury, and functional outcomes. Methods: We prospectively enrolled 200 patients with acute ischemic stroke who underwent EVT. Autoregulatory function was continuously measured for >=24 hours using simultaneous recordings of near-infrared spectroscopy and mean arterial pressure (MAP). The resulting autoregulatory index was used to calculate and trend the BP range at which autoregulation was most preserved. Percent time and “dose” that MAP exceeded the upper limit or dropped below the lower limit of autoregulation (ULA, LLA) were calculated for each patient. Hemodynamic parameters were correlated with short-term clinical endpoints (symptomatic ICH), biomarkers of secondary brain injury (net water uptake, hemorrhagic transformation (HT), infarct progression), and 90-day functional outcomes. Results: Personalized BP targets were successfully computed in 195 patients (mean age 70 ± 16, 45% female, mean NIHSS 14, mean monitoring time 31 ± 28 hours). Time above the ULA was associated with worse functional outcomes at 90-days after adjusting for age, sex, NIHSS, ASPECTS and TICI (adjusted OR per 10% increase 1.4, 95% CI 1.1-1.6, P=0.004). The burden of hyperperfusion was significantly greater among patients with HT (median 2.7 vs. 3.2 mmHg*min, p=0.01) and sICH (median 2.8 vs. 4.8 mmHg*min, p=0.05) than in those without it. Furthermore, time spent above the ULA was significantly correlated with net water uptake at 72 hours (r=0.37, p=0.03). Among patients with unsuccessful reperfusion, there was a non-significant correlation between time below the LLA and infarct progression (r=0.35, p=0.064). Conclusions: In the largest study conducted to date, deviations from personalized BP targets were associated with an increased risk of secondary brain injury and worse functional outcomes. Autoregulation-oriented BP management represents a promising strategy for maximizing recovery after ischemic stroke.