PURPOSE: The aim of this case-control study is to assess for predictive factors that may determine development of lateral compartment progression after Oxford medial unicompartmental knee replacement. METHODS: Twenty-eight patients who were revised as a result of lateral osteoarthritis progression were matched to 52 alive and unrevised patients. Body mass index, intra-operative findings, postoperative leg alignment, meniscal bearing size and histological findings have been analysed. Radiological analysis was carried out on the immediate postoperative radiographs by two blinded observers to assess the severity of arthritis in the lateral compartment. The measurements of the components positions were converted into binary figures as to whether they were inside or outside the recommended limits for analysis. Conditional logistic regression was used to identify important predictors of progression, taking into account the case-control grouping. RESULTS: The results shows that the condition of the lateral compartment is a significant predictor for developing subsequent lateral compartment arthrosis (OR 2.627, p = 0.019). The study showed no relationship between progression of arthritis and component position (OR [0.5-1.18], p [0.21-1]). Nor have it demonstrated that BMI (OR 1.06, p = 0.61), postoperative leg alignment (OR 1.26, p = 0.636), meniscal bearing size (1.32, p = 0.307) or presence of chondrocalcinosis (OR 0.35, p = 0.36) have any association with lateral osteoarthritis progression. CONCLUSIONS: This study showed the importance of excluding radiographic evidence of lateral compartment osteoarthritis on the preoperative radiograph prior to medial unicompartmental knee replacement. We have not been able to show any relationship between progression of arthritis and component position. Level of proof Case-control study, level III.