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Injuries to the anterior cruciate ligament are the most common surgically treated knee ligament injury. There is no consensus regarding the optimal graft choice between allograft and autograft tissue. Postoperative septic arthritis is an uncommon complication after anterior cruciate ligament reconstruction. The purpose of this study was to compare infection rates between procedures with use of allograft and autograft tissue in primary anterior cruciate ligament reconstruction.A combined prospective and retrospective multicenter cohort study was performed over a three-year period. Graft selection was determined by the individual surgeon. Inclusion and exclusion criteria were equivalent for the two groups (allograft and autograft tissue). Data collected included demographic characteristics, clinical information, and graft details. Patients were followed for a minimum of 5.5 months postoperatively. Our primary outcome was intra-articular infection following anterior cruciate ligament reconstruction.Of the 1298 patients who had anterior cruciate ligament reconstruction during the study period, 861 met the criteria for inclusion and formed the final study group. Two hundred and twenty-one patients (25.6%) received an autograft, and 640 (74.3%) received an allograft. There were no cases of septic arthritis in either group. The 95% confidence interval was 0% to 0.57% for the allograft group and 0% to 1.66% for the autograft group. The rate of superficial infections in the entire study group was 2.32%. We did not identify a significant difference in the rate of superficial infections between autograft and allograft reconstruction in our study group.While the theoretical risk of disease transmission inherent with allograft tissue cannot be eliminated, we found no increased clinical risk of infection with the use of allograft tissue compared with autologous tissue for primary anterior cruciate ligament reconstruction.Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.