BackgroundCollapse of the talus and peri-talar arthritis pose treatment challenges due to the anatomy and location of the talus as a keystone of the foot and ankle. Custom 3D-printed total talus replacement (TTR) and combined total ankle total talus replacement (TATTR) have emerged as treatment options for these pathologies. However, the safety and efficacy of these implants is unknown due to the limited number of cases and short follow-up durations. MethodsThis was a retrospective study to assess surgical outcomes of patients who underwent a TTR and TATTR with or without subtalar fusion. Patient demographics, intraoperative parameters, device related surgical and non-surgical events, imaging and clinical evaluations, and patient reported outcome (PRO) measures were compiled. ResultsA total of 38 patients received a custom 3D-printed implant with mean follow-up time of 22.1 (range: 12–45) months. In this cohort, 7 (18.4 %) required secondary surgery and 3 (7.9 %) required implant removal. Multivariate logistic regression revealed that patient diagnosis of depression was a significant predictor of secondary surgery with an OR 17.50 (p = 0.037). Significant postoperative improvements were observed in the talocalcaneal height (p = 0.005) and talar declination angle (p = 0.013) for the TATTR group. VAS and PROMIS pain interference (PI) scores demonstrated an initial significant improvement in pain, but this improvement did not maintain significance at most recent follow-up. However, there was a significant increase in the PROMIS physical function (PF) scores (p = 0.037) at most recent follow-up. ConclusionThese results demonstrate that TTR and TATTR provide significant improvement in post-operative radiographic foot and ankle alignment and physical function at the two-year timepoint. PRO findings suggest that patients are more active after surgery. Surgeons considering proceeding with either of these procedures should counsel patients about pain and functional outcomes as well as realistic expectations in patients with depression. Level of evidenceLevel 3