BACKGROUND: Apparent diffusion coefficient (ADC) thresholds are used to determine acute stroke lesion volume, but the reliability of this approach and comparability to the volume of the magnetic resonance diffusion-weighted imaging (MR-DWI) hyperintense lesion is unclear. METHODS: We prospectively recruited and clinically assessed patients who had experienced acute ischemic stroke and performed DWI less than 24 hours and at 3 to 7 days after stroke. We compared the volume of the manually outlined DW hyperintense lesion (reference standard) with lesion volumes derived from 3 commonly used ADC thresholds: .55 x 10(-3)/mm(2)/second(-1), .65 x 10(-3)/mm(2)/second(-1), and .75 x 10(-3)/mm(2)/second(-1), with and without “editing” of erroneous tissue. We compared the volumes obtained by reference standard, “raw,” and “edited” thresholds. RESULTS: Among 33 representative patients, the acute DWI lesion volume was 15,284 mm(3); the median unedited/edited ADC volumes were 52,972/2786 mm(3), 92,707/6,987 mm(3), and 227,681/unmeasureable mm(3) (.55 x 10(-3)/mm(2)/second(-1), .65 x 10(-3)/mm(2)/second(-1), and .75 x 10(-3)/mm(2)/second(-1) thresholds, respectively). Subacute lesions gave similar differences. These differences between edited and unedited diffusion-weighted imaging and ADC volumes were statistically significant. CONCLUSIONS: Threshold-derived ADC volumes require substantial manual editing to avoid over- or underestimating the visible DWI lesion and should be used with caution.