To improve the accuracy of the two-dimensional motion estimation of the common carotid artery (CCA) wall, a modified sub-pixel block matching method is proposed in this study. First, the directional asymmetric search (DAS) method is used for the block matching, and the sum of absolute error criterion combined with fuzzy set theory is used to determine the similar blocks. After obtaining the best block matching position, a combination of grid slope and parabolic interpolation (GS15PI) method is used for sub-pixel estimation. Then, the best matching position (point) obtained in the previous step and all points in its 3×3 neighborhood need to be determined. The blocks with the same size as the reference block centered on these points are used for block matching with the reference block from the search frame − 2. After obtaining the best block matching position, the GS15PI method is used for sub-pixel estimation. Finally, the average of sub-pixel positions obtained in the two previous steps is calculated as the final sub-pixel estimation. In simulation experiments, the two-dimensional motion errors of proposed method for simulated ultrasound sequences with the center frequencies of 5 MHz, 7.5 MHz, and 10 MHz are decreased by 8.41%,4.65%, and 11.25%, respectively, compared with the state-of-the-art method. In clinical experiments, as compared with the state-of-the-art method, the radial and longitudinal motion estimation results of proposed method are more consistent with the actual movement trend of the human CCA. In conclusion, the proposed method has good performance and can be used for motion estimation of the CCA wall in ultrasound images.