Category: Ankle Arthritis; Ankle Introduction/Purpose: There is limited evidence regarding risk factors for medial malleolar fractures after total ankle arthroplasty (TAA). A previous study showed that patients with medial pain following TAA had significantly thinner (<11mm) medial malleolar width, which has been used as a threshold for placing a prophylactic screw. However, this study included only six patients with pain over the medial malleolus. Other previously reported risk factors include coronal malalignment and poor bone quality. Therefore, this study examined the risk factors of postoperative medial malleolar stress fractures. In addition, we sought to assess the effect of the prophylactic screw placement. We hypothesized that a medial malleolar width <11mm and varus malalignment would be associated with increased fracture risk and that the prophylactic screw placement would be protective. Methods: A case-control study was conducted on 838 patients undergoing primary TAA between 2015 and. TAA revisions, arthrodesis takedowns, and intraoperative medial malleolar fractures were excluded. Demographic and surgical data were obtained. A total of 21 patients with postoperative medial malleolar stress fractures > 4 weeks postoperatively (cases) were identified through radiologic assessment (radiograph, CT, or MRI) and matched to a control group of 129 patients. Radiographic evaluation included pre- and post-TAA tibial coronal alignment, postoperative medial malleolar width at the tibial component, and prophylactic screw fixation. Demographics and radiographic variables were compared between cohorts using the Mann-Whitney U test for continuous variables and Pearson Chi-square for categorical variables. Logistic regression was used to investigate the association of medial malleolar stress fractures with gender, coronal tibial implant size, postoperative coronal alignment, prophylactic screw fixation, and medial malleolar width using odds ratios (OR), and standard error (SE). Results: Of 838 TAAs, 2.51% sustained a postoperative medial malleolar fracture (n = 21). Of these, 13/21 (61.9%) required reoperation: internal fixation (12) and TAA revision (1). Mean (SD) medial malleolar width was significantly smaller in the fracture cohort (8.62 mm [1.63]) than in controls (11.78mm [1.75]), P<0.001). Mean (SD) postoperative tibial component coronal alignment was 92.2º (2.82) for patients with medial malleolar fracture and 90.23º (1.68) for the control cohort (P = 0.003). Postoperative varus tibial component alignment (OR = 1.61 [95%CI 1.16 02 − 2.22], P = 0.004) and smaller medial malleolar width (OR = 0.11 [95% CI 0.04 02 − 0.3], P < 0.001) were associated with increased probability of a post-TAA medial malleolar fracture. Prophylactic screw fixation resulted in a 90% reduction in the odds of a fracture (OR = 0.10 [95%CI 0.02 02 − 0.64], P = 0.015). A medial malleolar width of 10.31 mm was identified as a threshold for predicting a medial malleolar stress fracture. Conclusion: In this study, the prevalence of postoperative periprosthetic fractures after TAA was similar to prior studies. Decreased medial malleolar thickness and postoperative varus malalignment were associated with an increased risk of a postoperative medial malleolar stress fracture. A malleolar width of 10.31 mm was identified as a potential threshold. Prophylactic medial malleolar screw fixation was protective and associated with a 90% reduction in fracture probability. Surgeons should consider prophylactic screw fixation patients with a medial malleolar width < 10.31 mm or at risk of postoperative varus deformity.