Purpose:To quantitatively assess whether decreasing total radiation dose of the image acquisition protocol has an effect on cerebral CT perfusion values in patients with acute stroke. Materials and Methods: This retrospective study was approved by the institutional ethics committee, and informed consent was waived. Twenty consecutive patients with ischemic stroke who underwent CT perfusion imaging with a 320AC/a,!aEURoedetector row CT scanner were included. A standard acquisition protocol was used, which was started 5 seconds after injection of a contrast agent, with a scan at 200 mAs, followed after 4 seconds by 13 scans, one every 2 seconds, at 100 mAs, and then five scans, one every 5 seconds, at 75 mAs. The total examination had an average effective dose of 5.0 mSv. For each patient, a patient-specific digital perfusion phantom was constructed to simulate the same protocol at a lower total dose (0.5AC/a,!aEURoe5.0 mSv, with stepped doses of 0.5 mSv). The lowest setting for which the maximum mean difference remained within 5% of the reference standard (at 5.0 mSv) was marked as the optimal setting. At the optimal setting, Pearson correlation coefficients were calculated to assess correlations with the reference values, and paired t tests were performed to compare the means. Results: At 2.5 mSv, the maximum mean differences in values from those of the reference standard were 4.5%, 5.0%, and 1.9%, for cerebral blood flow, cerebral blood volume, and mean transit time, respectively. Pearson correlation coefficients of perfusion values for white matter and gray matter were 0.864AC/a,!aEURoe0.917, and all differences were significant (P < .0001). Paired t tests showed no significant differences between the reference standard and optimal settings (P = .089AC/a,!aEURoe.923). Conclusion: The total dose of a clinical cerebral CT perfusion protocol can be lowered to 2.5 mSv, with only minor quantitative effects on perfusion values. Dose reduction beyond this point resulted in overestimation of perfusion values.