Background: Quantitative and qualitative evaluation of middle cerebral artery (MCA) density, together with extent of thrombi, was assessed on plain computerized tomography (CT) to delineate better the prognostic value of the hyperdense MCA sign (HMCAS) in a cohort of patients who underwent intravenous or intra-arterial thrombolysis. Methods: Density of MCA was quantified by maximum pixel-sized measurement of Hounsfield unit (HU) in 105 patients with acute MCA proximal segment occlusion, 15 patients with vertebrobasilar circulation stroke (VBS) and 44 nonstroke control subjects. Predictive value of HMCAS, absolute HU value of within MCA, side-to-side HU ratio, and difference along with a newly introduced hyperdense MCA burden score in early dramatic recovery (EDR) and third-month favorable prognosis were determined with multivariate adjustment for age, baseline stroke severity, and thrombus length as measured on CT angiography. Receiver operator characteristics (ROC) curves were used to determine the cutoffs of quantitative indices to determine HMCAS and their prognostic significance. Results: Higher HU was present in the ipsilateral MCA of the patients compared with their contralateral side and basilar tip and any MCA of VBS stroke and control subjects (area under the curve [AUC] of ROC curves was .753). Symptomatic-to-asymptomatic HU difference and ratio of MCA stroke were also significantly higher than side-to-side difference calculated in VBS stroke and control groups (AUC of ROC curves: .770 and .764, respectively). Optimal thresholds of absolute HU (44), side-to-side HU difference (2), and ratio (1.0588) showed borderline sensitivity and specificity. HMCAS and its quantitative indices were not significantly associated with EDR and favorable third-month outcome. Furthermore, there was no difference in terms of cardioembolic and atherothrombotic thrombi HU. Conclusions: Utility of the HMCAS as a prognostic marker in stroke thrombolysis is not high in the CT angiography era. Previous observation regarding its positive prognostic role can be attributed to its association with proximal location and extent of clot burden, which are detectable reliably with current CT angiography techniques. Neither quantification nor extent of increased density seems to have clinical utility for treatment decision making in MCA strokes and prediction of emboli composition and response to recanalization attempt.