The purpose of this study is to explore the biomechanical characteristics of the tibia after unicompartmental knee arthroplasty with different distributions of two-pin holes, and to optimize the two-pin holes scheme to reduce the risk of tibial fractures after unicompartmental knee arthroplasty. Lower limbs model is segmented and reconstructed from computed tomography images. Four combinations of two pin holes created for tibial cutting guide placement are simulated with finite element analysis. In the third mode, the positioning hole at the proximal medial edge of the tibial plateau has the highest stress value, and the position of the positioning hole near the medial edge of the proximal tibial plateau appears stress concentration. The present study revealed that placing tibial cutting guide holding pins centrally would lower the risks of periprosthetic fracture of the medial tibial plateau.