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Background and Purpose Ischemic lesion recurrence on diffusion-weighted imaging (DWI-LR) is a frequently observed phenomenon after acute ischemic stroke. However, no study has elucidated the impact of DWI-LR on functional outcome. Methods Among a consecutive series of patients who presented with focal symptoms or signs compatible with stroke within 48 hours from the onset over a 50-month period, those who had relevant ischemic lesions on initial DWI and underwent follow-up DWI within 14 days after the onset were enrolled in this study. As outcome variables, the scores on the modified Rankin Disability Scale (mRDS) at 3 months and 1 year were measured prospectively and dichotomized into good (0-2) vs. poor (3-6). When calculating odds ratios (ORs), adjustment was performed for age, previous stroke, initial score on the NIH Stroke Scale, stroke subtype, and IV thrombolysis. Results Among those 786 patients finally enrolled in this study, 221 (28.1%) had DWI-LR. For a poor outcome at 3 months, the crude ORs of any, symptomatic, and asymptomatic DWI-LR were 2.70 [95% confidence interval (CI), 1.96 to 3.72], 10.03 (95% CI, 4.39 to 22.96), and 2.04(95% CI, 1.44 to 2.88), respectively. With adjustment, the OR of symptomatic DWI-LR was 6.44(95% CI, 2.50 to 16.57), whereas those of any and asymptomatic DWI-LR lost their statistical significance: 1.44 (95% CI, 0.94 to 2.20) and 1.04 (95% CI, 0.65 to 1.65), respectively. Analyzing with the 1-year outcome produced similar results. Conclusions This study shows that symptomatic early lesion recurrence can affect functional outcome after acute ischemic stroke, whereas an asymptomatic one may not.