The present study investigated the effects of anteromedial (AM) and central femoral footprint placement on stress and strain distribution around the femoral and tibial tunnel and graft following anterior cruciate ligament reconstruction (ACLR). A three-dimensional (3D) reconstructed knee model was validated and used for simulating ACLR by finite element analysis. A combined loading during normal human walking was applied to the knee models using different anatomic femoral tunnel placement at 20° knee flexion. The results of von Mises stress and principal strain at the entrances of the femoral and tibial tunnel and ACL graft was determined. The peak von Mises stress and the maximum principal strain in the AM footprint group were 8.78 MPa and 8850.89 μ-strain at the entrance of femoral tunnel, and 5.29 MPa and 5553.27 μ-strain at the entrance of tibial tunnel. The results in the AM footprint group were higher than that in the central footprint group. The peak von Mises stress around the ACL graft following AM footprint ACLR was 28.63 MPa, higher than that following the central footprint ACLR. The AM footprint ACLR generated more significant peak von Mises stress and maximum principal strain around the entrances of femoral and tibial tunnel and the graft than the central footprint. The present results are of clinical relevance as they can provide a better understanding of tunnel enlargement and graft failure.