Rationale and Objectives: The preoperative assessment of tumor grade has important clinical implications for the treatment and prognosis of patients with colorectal adenocarcinomas. The purpose of this study is to investigate the predictive significance of colorectal adenocarcinoma grade using 256-slice whole-tumor computed tomography (CT) perfusion. Materials and Methods: Fifty-three patients with proven colorectal adenocarcinomas were enrolled. All of them underwent 256-slice whole-tumor CT perfusion. They were divided into two different subgroups according to postoperative pathological results: low grade and high grade. The Kruskal-Wallis test or one-way analysis of variance was used for comparison of CT perfusion parameters between different tumor grades. Multivariant correlation between pathologic tumor stage, histologic tumor differentiation, and whole-tumor CT perfusion parameters was evaluated by Spearman rank correlation coefficient. According to receiver operating characteristic (ROC) curves, perfusion parameters including blood flow (BF), peak enhancement index (PEI), blood volume (BV), and time to peak (UP) of 53 patients were analyzed, and the sensitivity, specificity, and accuracy of these parameters in predicting tumor grade were calculated. Results: There were significant differences in BF and UP between low-grade and high-grade tumors. According to the ROC curve, BF and TTP were of diagnostic significance, with the area under the curve values of 0.828 and 0.736, respectively. The diagnostic threshold of BF was 32.12 mL/min/100 g and that of TTP was 18.10 seconds. Conclusions: The CT perfusion parameters (BF, TTP) of first-pass 256-slice whole-tumor CT perfusion imaging can reflect tumor grade in colorectal adenocarcinoma.