A computational framework was used to simulate the anterior Cruciate ligament (ACL) reconstructive surgeries, by virtually removing the ACL and then modeling the surgical preparation, tunnel architecture, graft pre-tensioning and fixation angle of a bone-patellar-tendon-bone autograft. To evaluate the relative influence of these surgical factors on the intraoperative joint response a global sensitivity analyses were performed with 48 models. The sensitivity results indicated that the combined variation in tunnel architecture and graft pre-tension at the time of fixation accounts for most of the estimated variance of the two outcomes. Data derived from the 48 ACL reconstructed models indicated that the anatomic surgical design may not be the only design that recovers the healthy joint laxity. In the context of the design of prospective studies, our findings highlight the need to include the graft tension at the time of fixation as a variable in the evaluation of the surgery.