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Introduction: Failure of alloplastic breast reconstruction is an uncommon occurrence that may result in abandonment of reconstructive efforts or salvage with conversion to autologous reconstruction. The purpose of this study was to identify factors that predict failure of alloplastic breast reconstruction and conversion to autologous reconstruction. Methods: A retrospective chart review was conducted of patients who underwent mastectomy and immediate alloplastic breast reconstruction between 2008 and 2019. Inclusion criteria included patients 18 years or older who underwent initial alloplastic reconstruction with a minimum of 3-year follow-up. Data collected included age, body mass index, cancer type, surgical characteristics, neo/adjuvant treatment details, and complications. Results were analyzed using Fischer's exact test, t -test, and multivariate logistic regression. Results: A total of 234 patients met inclusion criteria. Of those, 23 (9.8%) required conversion from alloplastic to autologous reconstruction. Converted patients had a mean age of 50.1 ± 8.5. The time from initial alloplastic reconstruction to conversion was 30.7 months. The most common reasons for conversion included soft tissue deficiency (48%), infection (30%), and capsular contracture (22%). Patients were converted to deep inferior epigastric perforator flap (DIEP; 52%), latissimus dorsi flap with implant (26%), and DIEP with implant (22%). Multivariate logistic regression modeling identified radiation (OR 8.4 [CI = 1.7-40.1]) and periprosthetic infection (OR 14.6 [CI = 3.4-63.8]) as predictors for conversion. Conclusions: Among patients undergoing mastectomy with immediate alloplastic breast reconstruction, those treated with radiation have 8.4 greater odds of conversion and those with a periprosthetic infection have 14.6 greater odds for conversion to an autologous reconstruction., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)