Digital tomosynthesis (DTS) is a method to reconstruct pseudo three-dimensional (3D) volume images from two-dimensional x-ray projections acquired over limited scan angles. Compared with cone-beam computed tomography, which is frequently used for 3D image guided radiation therapy, DTS requires less imaging time and dose. Successful implementation of DTS for fast target localization requires the reconstruction process to be accomplished within tight clinical time constraints (usually within 2 min). To achieve this goal, substantial improvement of reconstruction efficiency is necessary. In this study, a reconstruction process based upon the algorithm proposed by Feldkamp, Davis, and Kress was implemented on graphics hardware for the purpose of acceleration. The performance of the novel reconstruction implementation was tested for phantom and real patient cases. The efficiency of DTS reconstruction was improved by a factor of 13 on average, without compromising image quality. With acceleration of the reconstruction algorithm, the whole DTS generation process including data preprocessing, reconstruction, and DICOM conversion is accomplished within 1.5 min, which ultimately meets clinical requirement for on-line target localization.