Rationale and Objectives: To evaluate the improvements in measurements of blood flow (BF), blood volume (BV), and permeability-surface area product (PS) after principal component analysis (PCA) filtering of computed tomography (CT) perfusion images. To evaluate the improvement in CT perfusion image quality with poor contrast-to-noise ratio (CNR) invivo. Materials and Methods: A digital phantom with CT perfusion images reflecting known values of BF, BV, and PS was created and was filtered using PCA. Intraclass correlation coefficients and Bland-Altman analysis were used to assess reliability of measurements and reduction in measurement errors, respectively. Rats with C6 gliomas were imaged using CT perfusion, and the raw CT perfusion images were filtered using PCA. Differences in CNR, BF, BV, and PS before and after PCA filtering were assessed using repeated measures analysis of variance. Results: From simulation, mean errors decreased from 12.8 (95% confidence interval [CI]=-19.5 to 45.0) to 1.4mL/min/100 g (CI=-27.6 to 30.4), 0.2 (CI=-1.1 to 1.4) to -0.1mL/100 g (CI=-1.1 to 0.8), and 2.9 (CI = -2.4 to 8.1) to 0.2mL/min/100 g (CI=-3.5 to 3.9) for BF, BV, and PS, respectively. Map noise in BF, BV, and PS were decreased from 51.0 (CI=-3.5 to 105.5) to 11.6mL/min/100 g (CI=-7.9 to 31.2), 2.0 (CI=0.7 to 3.3) to 0.5mL/100 g (CI=0.1 to 1.0), and 8.3 (CI=-0.8 to 17.5) to 1.4mL/min/100 g (CI=-0.4 to 3.1), respectively. For experiments, CNR significantly improved with PCA filtering in normal brain (P<.05) and tumor (P<.05). Tumor and brain BFs were significantly different from each other after PCA filtering with four principal components (P<.05). Conclusions: PCA improved image CNR invivo and reduced the measurement errors of BF, BV, and PS from simulation. A minimum of four principal components is recommended. © 2014 AUR.