Studies evaluating the effect of reperfusion on ischemic edema in acute stroke described conflicting results. Net water uptake (NWU) per brain volume is a new quantitative imaging biomarker of space-occupying ischemic edema, which can be measured in computed tomography (CT). We sought to investigate the effects of vessel recanalization on the formation of ischemic brain edema using quantitative NWU. In this multicenter observational study, acute ischemic stroke patients with a large vessel occlusion (LVO) in the anterior circulation were consecutively screened. Patients with vessel recanalization (thrombolysis in cerebral infarction (TICI) 2 b or 3) versus persistent vessel occlusion (no thrombectomy, TICI 0-1) were compared. Lesion-NWU was quantified in multimodal admission CT and follow-up CT (FCT), and ΔNWU was calculated as difference. Of 194 included patients, 150 had successful endovascular recanalization and 44 persistent LVO. In FCT after treatment, the mean (standard deviation) ΔNWU was 15.8% (5.7) in patients with persistent LVO and 9.8% (5.8) with vessel recanalization ( p < 0.001). In multivariate regression analysis, vessel recanalization was independently associated with a lowered ΔNWU by 6.3% compared to LVO (95% confidence interval: 3.7–9.0, p < 0.001). Successful vessel recanalization was associated with a significantly reduced formation of ischemic brain edema. Quantitative NWU may be used to compare the treatment effects in acute stroke.