Background: Underlying factors contributing to increased risk of graft rupture after anterior cruciate ligament reconstruction (ACLR) are not well described. Objective: To systematically review intrinsic risk factors for sustaining a graft rupture. Design: A systematic review with meta-analysis according to the PRISMA guidelines. Four databases (MEDLINE, CINAHL, EMBASE, Sport Discus) were searched from inception to January 2020. Meta-analyses (random effect model) were performed and expressed as odds ratios (OR). Setting: The included studies describe a variety of sport settings and activity levels. Participants: The review comprises studies including males and/or females of any age who have had ACLR. Assessment of Risk Factors: All longitudinal studies investigating any intrinsic risk factor for future graft rupture were included. Main Outcome Measurements: Graft rupture. Results: Seventy-seven studies were eligible for meta-analysis. The following factors all independently increased the odds of sustaining a graft rupture after ACLR: Age ≤ 18 years (OR: 3.87, 95% CI: 2.32–6.46), higher pre-primary injury activity level (OR: 2.43, 95% CI: 1.56–3.82), family history of ACL injury (OR: 1.98, 95% CI: 1.50–2.62), returning to a high activity level (OR: 1.87, 95% CI: 1.11–3.15), and increased lateral tibial slope (OR: 1.64, 95% CI: 1.13–2,38). None of the following factors were found to be associated with future graft rupture; sex, smoking status, generalized joint laxity, timing of surgery or return to sport (RTS), playing soccer compared to other sports, hop performance at time of RTS or concomitant meniscal or collateral ligament injuries. Conclusions: Young age, family history of ACL injury, high tibial slope and previous and current high activity level should be considered when screening for increased risk of graft rupture following ACLR. Future studies on the possible role of sensorimotor factors, e.g., muscle activation and/or strength and proprioception for future graft ruptures are warranted.