PurposeIn modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction.MethodsWe conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention.ResultsFrom 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33–2.24;p< 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57–3.20;p< 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06–3.12,p=0.030), explant (aOR, 3.34; 95% CI, 3.85–7.83,p< 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88–3.43,p< 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction.ConclusionOur study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered withNCT04783818, and the date of registration is 1 March, 2021, retrospectively registered.