BACKGROUND Our objective was to establish and compare three-dimensional models of knee joints of mini-pigs and sheep, the 2 most commonly used animal models of osteoarthritis. MATERIAL AND METHODS Three-dimensional geometric models of knee joints were used to assess their biomechanical properties by analysis of the three-dimensional finite element stress load for flexion at 30° and 60°. RESULTS Analysis of multiple tissues indicated that the sheep knee had greater stress peaks than the mini-pig knee at 30° flexion (range: 12.5 to 30.4 Mpa for sheep vs. 11.1 to 20.2 Mpa for mini-pig) and at 60° flexion (range: 17.9 to 43.5 Mpa for sheep vs. 15.9 to 28.9 Mpa for mini-pig). In addition, there was uneven distribution of stress loads in the surrounding ligaments during flexion. CONCLUSIONS Our three-dimensional finite element analysis indicated that the mini-pig knee joint had stress values and changes of cartilage, meniscus, and peripheral ligaments that were similar to those of the human knee.