ObjectiveTo investigate the risk factors of contralateral anterior cruciate ligament (ACL) injury after primary ACL reconstruction. Methods A retrospective review was conducted on the 716 patients with ACL injury who received primary ACL reconstruction surgery and met the selection criteria between January 2012 and September 2018. After a mean follow-up period of 7.6 years (range, 4-10 years), 65 patients (9.1%) experienced contralateral ACL injury (injured group) and 651 patients (90.9%) did not (uninjured group). There was no significant difference in age, body mass index, and preoperative Lachman test degree between groups (P>0.05). However, the proportion of female in the injured group was significantly higher than that of male (P<0.05), and the preoperative posterior tibial slope (PTS) was significantly higher than that of the uninjured group (P<0.05). Using the outcome of contralateral ACL injury as the dependent variable, the clinical data of the patient was first used as the independent variable, and univariate COX regression was used to analyze the prognostic influencing factors. Then, the indicators with differences in univariate COX regression were used as the independent variable, and multivariate COX regression was used to analyze the independent risk factors affecting prognosis. Log-Rank (Mantel-Cox) test was used to test and analyze the occurrence time of contralateral ACL injury in patients of different genders; X-tile software was used to analyze the occurrence time of contralateral ACL injury in patients with different PTS using Log-Rank (Mantel-Cox) test and PTS cut-off values. ResultsUnivariate COX regression analysis showed that gender and PTS were influence factors for contralateral ACL injury (P<0.05); further multivariate COX regression analysis showed that female and increased PTS were independent risk factors for contralateral ACL injury (P<0.05). The Log-Rank (Mantel-Cox) test results showed that the contralateral ACL injury occurred in female at 8.853 (8.600, 9.106) years, which was significantly shorter than that in male [9.661 (9.503, 9.819) years] (χ2=20.323, P<0.001). Using X-tile software to analyze the cut-off value of PTS, it was found that the cut-off value of PTS for contralateral ACL injury was 10.92°. According to the Log-Rank (Mantel-Cox) test, it was found that the contralateral ACL injury occurred in 5.762 (4.981, 6.543) years in patients with PTS≥10.92°, which was significantly shorter than patients with PTS<10.92° [9.751 (9.650, 9.853) years](χ2=302.479, P<0.001). ConclusionFemale and PTS≥10.92° after primary ACL reconstruction are independent risk factors for contralateral ACL injury.