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Category: Ankle; Ankle Arthritis; Trauma Introduction/Purpose: Tibiotalocalcaneal (TTC) arthrodesis is a routinely utilized salvage procedure that treats patients with severe talar and subtalar joint disease. Unfortunately, nonunion is a relatively common complication postoperatively which can increase risks and costs for patients. The goal of this study is to review the literature to identify risk factors for nonunion post TTC arthrodesis and stratify them based on strength of evidence. A meta-analysis will be performed on risk factors when appropriate to establish values based on pre-existing studies. Methods: Five databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, and Web of Science) were searched from inception to May 17th, 2020. Two independent reviewers screened abstracts and full-text articles for those that included risk factors predictive of nonunion for TTC arthrodesis. Any disagreements were discussed between the two reviewers and a third reviewer served as the ultimate decision maker if a consensus could not be reached. Relevant data regarding participants’ characteristics, study design, follow-up time, statistical tests and identified risk factors were extracted from the included studies. The two reviewers independently appraised the methodological quality of the studies using the Quality In Prognosis Studies tool. Those risk factors described in multiple studies were included in the meta-analysis. Random effects meta-analyses were summarized as forest plots of individual study and pooled random effect results. Results were reported as odds ratios (OR) with 95% confidence intervals (CI). Results: Database search identified 428 articles, of which 113 were screened for full text. Eight studies involving 607 patients were included and 33 potential risk factors for nonunion were identified. Risk factors were stratified into demographic, preoperative, intraoperative and postoperative. Results of the meta-analysis established two significant risk factors for nonunion following TTC arthrodesis. Strong evidence supports that prior neurological deficits, such as Charcot neuroarthropathy and diabetes neuropathy, are associated with nonunion following surgery (OR: 2.86, 95% CI: 1.56 - 5.23). There was moderate evidence to suggest that preoperative infection was predictive for nonunion (OR: 3.99, 95% CI: 1.26 - 12.68). Although our meta- analysis did not find smoking (OR: 1.75, 95% CI: 0.90 - 3.38) or diabetes (OR: 2.28, 95% CI: 0.98 - 5.34) to be significant risk factors, multiple high quality studies support these as comorbidities that increase the likelihood of nonunion. Conclusion: TTC arthrodesis can be an effective salvage procedure but is associated with high nonunion rates. The results of our meta-analysis suggest that prior neurological deficits, such as Charcot neuroarthropathy or diabetes neuropathy, have strong evidence for failure to achieve union. Although our meta-analysis did not find other statistically significant risk factors, the findings of individual studies in our review suggest that diabetes mellitus and smoking are both factors which can lead to failure of fusion. Surgeons should be cognizant of these risks when performing TTC arthrodesis and carefully monitor patients with the aforementioned comorbidities to achieve successful results.