In this paper, we present a direct image registration approach that uses mutual information (MI) as a metric for alignment. The proposed approach is robust and gives an accurate estimation of a set of 2-D motion parameters in real time. MI is a measure of the quantity of information shared by signals. Although it has the ability to perform robust alignment with illumination changes, multimodality, and partial occlusions, few works have proposed MI-based applications related to spatiotemporal image registration or object tracking in image sequences because of some optimization problems, which we will explain. In this paper, we propose a new optimization method that is adapted to the MI cost function and gives a practical solution for real-time tracking. We show that by refining the computation of the Hessian matrix and using a specific optimization approach, the registration results are far more robust and accurate than the existing solutions, with the computation also being cheaper. A new approach is also proposed to speed up the computation of the derivatives and keep the same optimization efficiency. To validate the advantages of the proposed approach, several experiments are performed.