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.