Purpose: Compare alterations in running mechanics during maximal treadmill sprints of different distances. Methods: Eleven physically active males performed short (100-m), medium (200-m) and long (400-m) running sprints on an instrumented treadmill. Continuous measurement of running kinetics/kinematics and spring-mass characteristics were recorded and values subsequently averaged over every 50-m distance intervals for comparison. Results: Compared with the initial 50 m, running velocity decreased (P<0.001) by 8±2%, 20±4% and 39±7% at the end of the 100, 200 and 400-m, respectively. All sprint distances (except for step length in the 100-m) induced significantly longer (P<0.05) contact times (+7±4%, +22±8% and +36±13%) and lower step lengths (-1±4%, -5±5% and -41±2%) and frequencies (-6±3%, -13±7% and -22±8%) at the end of the 100-m, 200-m and 400-m, respectively. Larger reductions in ground reaction forces occurred in horizontal versus vertical direction, with greater changes with increasing sprinting distance (P<0.05). Similarly, the magnitude of decrement in vertical stiffness increased with sprint distance (P<0.05), while leg stiffness decreases were smaller and limited to 200-m and 400-m runs. Overall, we observed earlier and larger alterations for the 400-m compared with other distances. Conclusions: The magnitude of changes in running velocity and mechanics over short (100-m), medium (200-m) and long (400-m) treadmill sprints increases with sprint distance. The alterations in stride mechanics occur relatively earlier during the 400-m compared with the 100-m and 200-m runs.