Piles are widely used to reinforce slopes. Uncertainties exist in stability with anti-slide pile reinforced slope due to the uncertainties of soil. Reliability method can be used to quantify the uncertainties. Shear strength reduction method is employed to obtain the factor of safety and slip surfaces with different pile reinforcement locations. A response surface method-based first order reliability method is used to calculate the failure probability. Based on FLAC3D, an automatic programing procedure is proposed for convenient application.Steel pipe piles are adopted for stabilization in the illustrative example. The results show pile location and spacing have significant effect on the reliability of the illustrative example. An optimal location may exist at a certain spacing for the illustrative example. The suggested method can be helpful for the optimal design of pile reinforcement for soil slopes.