<i>Background:</i> The intention of this study was the prospective analysis of Wallerian degeneration of the pyramidal tract after paramedian pons infarction. <i>Methods:</i> Patients with paramedian pons infarct underwent MR imaging including diffusion tensor imaging at admission and got 1–3 MR scans up to 6 months of follow-up. Clinical scores and transcranial magnetic stimulation were acquired in the acute phase and 3–6 months later. The pyramidal tracts were manually segmented in fractional anisotropy (FA) color maps after coregistration of all MR datasets of each patient. FA as well as axial and radial diffusivity were measured in the volume of lesioned and contralateral pyramidal tracts distally to the ischemic lesion. <i>Results:</i> From 11 patients studied, 7 developed Wallerian degeneration detected as statistically significant decrease in FA over time in the distal pyramidal tract. Wallerian degeneration could be detected at the earliest between the first and the third days after the onset of symptoms. A continuous decrease in FA and an increase in axial and radial diffusivity in degenerating pyramidal tracts over time were demonstrated. A significant correlation between NIHSS score on admission and the slope of relative axial diffusivity and a significant correlation between motor-evoked potential amplitudes of the arm on admission and the outcome relative FA was found. <i>Conclusions:</i> The initial MR image cannot predict the following Wallerian degeneration. However, the severity of motor disturbance and the motor-evoked potential of the arm on admission could be possible parameters to predict Wallerian degeneration. For estimation of Wallerian degeneration over time, at least 2 diffusion tensor imaging measurements have to be done at different time points.