ObjectiveTo identify and quantify potential risk factors for osteoarthritis (OA) following traumatic knee injury.DesignSystematic review and meta-analyses that estimated the odds of OA for individual risk factors assessed in more than four studies using random-effects models. Remaining risk factors underwent semiquantitative synthesis. The modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for prognostic factors guided the assessment.Data sourcesMEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to 2009–2021.EligibilityRandomised controlled trials and cohort studies assessing risk factors for symptomatic or structural OA in persons with a traumatic knee injury, mean injury age ≤30 years and minimum 2-year follow-up.ResultsAcross 66 included studies, 81 unique potential risk factors were identified. High risk of bias due to attrition or confounding was present in 64% and 49% of studies, respectively. Ten risk factors for structural OA underwent meta-analysis (sex, rehabilitation for anterior cruciate ligament (ACL) tear, ACL reconstruction (ACLR), ACLR age, ACLR body mass index, ACLR graft source, ACLR graft augmentation, ACLR+cartilage injury, ACLR+partial meniscectomy, ACLR+total medial meniscectomy). Very-low certainty evidence suggests increased odds of structural OA related to ACLR+cartilage injury (OR=2.31; 95% CI 1.35 to 3.94), ACLR+partial meniscectomy (OR=1.87; 1.45 to 2.42) and ACLR+total medial meniscectomy (OR=3.14; 2.20 to 4.48). Semiquantitative syntheses identified moderate-certainty evidence that cruciate ligament, collateral ligament, meniscal, chondral, patellar/tibiofemoral dislocation, fracture and multistructure injuries increase the odds of symptomatic OA.ConclusionModerate-certainty evidence suggests that various single and multistructure knee injuries (beyond ACL tears) increase the odds of symptomatic OA. Risk factor heterogeneity, high risk of bias, and inconsistency in risk factors and OA definition make identifying treatment targets for preventing post-traumatic knee OA challenging.