Critical safety wheel wear size is investigated through considering the fatigue safety effect on RD2 type axle of China railway freight cars. The wheel wear size increase results in a rise of the wheel-rail contact forces, which increase the fatigue stress history of the axle in service. Therefore, the size must be controlled to maintain the axle safety in service before the next overhaul inspection. A field investigation was firstly made on the wear size change regularity. Then, the size related wheel-rail impact forces are solved by a non-linear Hertzian contact theory with a vehicle multi-body dynamic model. In addition, a statistical method is further developed for incorporating the impact forces into the wheelset service load history. Finally, a wear size related critical state equation is established for ensuring the axle safety in service. A stationary solution is statistically obtained for the critical wear sizes with respect to the axle circumferential crack and semi-elliptical crack. It is concluded that the critical safety wear size should be controlled in the range of 100 mm at the statistical level of survival probability 0.99 and confidence 95%.