Purpose The aim of this systematic review was to evaluate the evidence on the existence of midflexion instability in primary total knee arthroplasty and which factors might contribute to this condition. Methods A comprehensive search of PubMed, Medline, Cochrane, CINAHL, and Embase databases was conducted since the inception of the database to July 2019. All relevant articles were retrieved, and their bibliographies were hand searched for further references on midflexion instability in primary total knee arthroplasty. The search strategy yielded 28 articles. After duplicate removal titles, abstracts and full text were reviewed. Fifteen studies were assessed for eligibility, 8 studies were excluded because they did not fully comply with the inclusion criteria. Seven articles were finally included in this systematic review. Anteroposterior translation, total knee arthroplasty design such as posterior-stabilized or posterior-cruciate-retaining total knee arthroplasty, joint line position with posterior condylar offset and joint gaps were considered to significantly influence midflexion stability. Results Based on this systematic review anteroposterior translation of ≥ 7 mm was an independent risk factor for midflexion instability at 30° knee flexion. Joint line position can be altered by up to 5 mm without measurable changes in joint stability and both an increase and a decrease in posterior condylar offset led to 30° midflexion instability. Conclusion Midflexion instability in primary total knee arthroplasty remains to be not entirely understood. Due to the low quality of available evidence, it is difficult to make any definitive conclusions. The factors which can lead to this condition were analyzed in this review, furthermore, we did not find exhaustive evidence on midflexion instability existence as an isolated entity. Nonetheless, this review will form a baseline for future research and creates awareness for the routine assessment of midflexion instability in primary total knee arthroplasty. Level of evidence IV.