INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has advantages over total knee arthroplasty including fewer complications and faster recovery; however, UKAs also have higher revision rates. Understanding reasons for UKA failure may, therefore, allow for optimized clinical outcomes. We aimed to identify failure modes for medial UKAs, and to examine differences by implant bearing, cement use and time. MATERIALS AND METHODS: A systematic review was conducted by searching MedLine, EMBASE, CINAHL and Cochrane databases from 2000 to 2020. Studies were selected if they included ≥ 250 participants, ≥ 10 failures and reported all failure modes of medial UKA performed for osteoarthritis (OA). RESULTS: A total of 24 cohort and 2 registry-based studies (levels II and III) were selected. The most common failure modes were aseptic loosening (24%) and OA progression (30%). Earliest failures (< 6 months) were due to infection (40%), bearing dislocation (20%), and fracture (20%); mid-term failures (> 2 years to 5 years) were due to OA progression (33%), aseptic loosening (17%) and pain (21%); and late-term (> 10 years) failures were mostly due to OA progression (56%). Rates of failure from wear were higher with fixed-bearing prostheses (5% cf. 0.3%), whereas rates of bearing dislocations were higher with mobile-bearing prostheses (14% cf. 0%). With cemented components, there was a high rate of failure due to aseptic loosening (27%), which was reduced with uncemented components (4%). CONCLUSIONS: UKA failure modes differ depending on implant design, cement use and time from surgery. There should be careful consideration of implant options and patient selection for UKA.