OBJECTIVES: Chondrolysis is defined as the rapid and diffuse loss of articular cartilage, typically within 12 months after surgery.  Although described in nearly all diarthroidial joints, recent studies have shown that chondrolysis has been misdiagnosed in numerous case reports. This study aimed to determine contributing factors associated with the misdiagnosis of chondrolysis to help improve accurate diagnostication and clinical decision making.  METHODS: A systematic literature review identified 128 publications on 783 joints (626 hips, 128 shoulders, and 29 knees) diagnosed as chondrolysis.  Among these, 72 joints (48% knees, 9% shoulders, and 7% hips) were determined to be misdiagnosed by consensus across five orthopaedic surgeons.  A broad range of data was examined in relation to misdiagnosis.  For all cases, the presenting diagnosis and surgical procedure(s) as well as other potential contributors including chemical, thermal, and mechanical factors were examined to estimate the differential risk of rapidly developing osteoarthritis which was categorized as low, moderate, or high.  Descriptive statistics, bivariate comparisons, and multivariate regression analyses were performed, with p<0.05 denoting significance.  RESULTS: Misdiagnosis of chondrolysis was neither associated with arthroscopic procedures nor chemical, thermal, or mechanical factors during surgery.  Among correctly diagnosed cases, the risk of developing rapid osteoarthritis was considered low among 94.4% (671/711), moderate among 1.0% (7/711), and high among 4.6% (33/711).  In contrast, among misdiagnosed cases, 13.9% (10/72) of presenting diagnoses were considered low risk for osteoarthritis, 19.4% (14/72) moderate, and 66.7% (48/72) high.  After adjusting for potential confounders, the single most significant predictor associated with misdiagnosis of chondrolysis was a presenting medical condition that increased the risk of developing rapid osteoarthritis (p<0.01).  CONCLUSIONS: Misdiagnosis of chondrolysis appears to be strongly correlated with the risk of rapidly developing osteoarthritis, a pathology that is characterized by chronic and focal degeneration of cartilage rather than rapid and diffuse cartilage loss that signify chondrolysis.