Purpose To compare the mechanical stress applied to our grafted defect area according to the diameter of the plugs used in the treatment of osteochondral lesion with osteochondral autograft transplantation (OAT) procedure. Methods A biomechanical study was conducted on eight cadaveric knees. A 20-mm defect was created in the weight-bearing zone on the medial femoral condyle then filled either with three plugs of 8 mm, or with four plugs of 6 mm, or with 6 plugs of 4 mm diameter. After the preparation of the specimens, each knee was installed on a mechanical test bench (Instron 5566A). A continuous axial compression of 700 N at 10 mm.min−1 was exerted on the joint. A K-scan 4000-type pressure sheet was used to record the contact area (mm2), the mean pressure (MPa), and the maximum pressure (MPa) on the area of interest. Results The differences found between the conditions were not statistically significant but showed tendencies. Filling the defect with six plugs of 4 mm restores a larger contact surface compared with the other plugs. The use of 8- and 6-mm grafts lead to a respective increase of 12% and 52% of the mean pressure compared with the 4 mm grafts. This difference was also found for the maximum pressure (36% and 129%). Regardless of the diameter of the plugs used, filling the lesion reduces the mean pressure exerted on the healthy cartilage by 19%. Discussion A trend emerged towards a better restoration of the cartilage surface and a more harmonious distribution of the pressures exerted in favour of the grafts of smaller diameter. A larger study is needed to obtain a statistically significant result.