Background: There is limited knowledge about which risk factors that contribute to the high numbers of contra-lateral anterior cruciate ligament (C-ACL) injury after primary ACL injury. Objective:  To systematically review intrinsic risk factors for sustaining a C-ACL injury. 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 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 with ACL injury. Assessment of Risk Factors: The review comprises longitudinal studies investigating any intrinsic risk factor for future C-ACL injury. Main Outcome Measurements: C-ACL injury Results: Thirty-five moderate-to-high quality studies were eligible for meta-analysis, including up to ~59 000 individuals. The following factors all independently increased the odds of sustaining a C-ACL: Returning to a high activity level (OR: 3.26, 95% CI: 2.10–5.06), BMI < 25 (OR: 2.73, 95% CI: 1.73–4.36), Age ≤ 18 years (OR: 2.42, 95% CI: 1.51–3.88), Family history of ACL injury (OR: 2.07, 95% CI: 1.54–2.80), Primary ACL reconstruction performed ≤ 3 months post injury (OR: 1.65, 95% CI: 1.32–2.06), Female sex (OR: 1.35, 95% CI: 1.14–1.61) and Concomitant meniscal injury (OR 1.21, 95% CI: 1.03–1.42). There were no associations between the odds of sustaining a C-ACL injury and Smoking status, Pre-injury activity level, Playing soccer compared to other sports or Timing of return to sport. Conclusions: Demographic factors such as female sex, young age and family history of ACL injury, as well as early reconstruction and returning to a high activity level all contribute to the risk of sustaining a C-ACL injury. Studies on modifiable sensorimotor risk factors are warranted.