Background The geometry of the tibial plateau has been largely ignored as a source of possible risk factors for anterior cruciate ligament injury. Discovering the anterior cruciate ligament injury risk factors associated with the tibial plateau may lead to delineation of the existing sex-based disparity in anterior cruciate ligament injuries and help develop strategies for the prevention of anterior cruciate ligament injuries regardless of gender. Hypothesis Individuals with a shallower medial tibial depth of concavity, while having increased posteriorly directed slope of their tibial plateau, are at increased risk of suffering an anterior cruciate ligament injury compared with those with decreased posterior slope and increased medial tibial depth. Furthermore, these relationships are different between men and women. Study Design Case-control study (prevalence); Level of evidence, 3. Methods The medial, lateral, and coronal tibial plateau slopes as well as the medial tibial depth of concavity in 55 uninjured controls (33 women and 22 men) and 49 anterior cruciate ligament—injured cases (27 women and 22 men) were measured using magnetic resonance images. First, a preliminary t test was performed to establish any existing differences between groups. Next, a logistic regression model was developed to determine the probability of anterior cruciate ligament injury in an individual based on the measured covariates. Results The female anterior cruciate ligament—injured cases had increased lateral tibial slope (P = .03) and shallower medial tibial depth (P = .0003) compared with the uninjured controls, while male cases had increased lateral and medial tibial slope (P = .02) and shallower medial tibial depth (P = .0004) compared with controls. The logistic regression analysis and odds ratio estimates showed that medial tibial depth is an important risk factor (odds ratio = 3.03 per 1 mm decrease in its value), followed by lateral tibial slope (odds ratio = 1.17 per 1° increase in its value) in all participants. The medial tibial slope (odds ratio = 1.18 per 1° increase in its value) was a risk factor only in men. Conclusion A combination of increased posterior-directed tibial plateau slope and shallow medial tibial plateau depth could be a major risk factor in anterior cruciate ligament injury susceptibility regardless of gender. Different injury risk models may be needed for men and women as other key risk factors are identified.