Background and Purpose— Our aim was to explore whether the mismatch in lesion visibility between b1000 and b0 images is an alternative to mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery imaging as a surrogate marker of stroke age. Methods— We analyzed patients from the European multicenter I-KNOW database. Independent readers assessed the visibility of ischemic lesions of the anterior circulation on b0 and fluid-attenuated inversion recovery imaging images. The signal-intensity ratio for b0 and fluid-attenuated inversion recovery imaging images was also measured from the segmented stroke lesion volume on b1000 images. Results— This study included 112 patients (68 men; mean age, 67.4 years) with stroke onset within (n=85) or longer than (n=27) 4.5 hours. b1000–b0 mismatch identified patients within 4.5 hours of stroke onset with moderate sensitivity (72.9%; 95% confidence interval [CI], 63.5–82.4) and specificity (70.4%; 95% CI, 53.2–87.6), high positive predictive value (88.6%; 95% CI, 81.1–96.0), and low negative predictive value (45.2%; 95% CI, 30.2–60.3). Global comparison of b1000–b0 mismatch with diffusion-weighted imaging–fluid-attenuated inversion recovery imaging mismatch (considered the imaging gold standard) indicated high sensitivity (85.9%; 95% CI, 78.2–93.6), specificity (91.2%; 95% CI, 76.3–98.1), and positive predictive value (96.7%; 95% CI, 88.0–99.1) and moderate negative predictive value (73.8%; 95% CI, 60.5–87.1) of this new approach. b0 signal-intensity ratio ( r =0.251; 95% CI, 0.069–0.417; P =0.008) was significantly although weakly correlated with delay between stroke onset and magnetic resonance imaging. Conclusions— b1000–b0 mismatch may identify patients with ischemic stroke of the within 4.5 hours of onset with high positive predictive value, perhaps constituting an alternative imaging tissue clock.