ObjectiveTo compare the survival outcomes in locally advanced breast cancer (LABC) patients receiving post-mastectomy radiotherapy (PMRT) with and without immediate breast reconstruction.MethodsWe used the Surveillance, Epidemiology, and End Results program to include LABC patients who were treated/not treated with immediate breast reconstruction followed by PMRT between 2003 and 2010. Statistical analysis was performed using the chi-squared test, Kaplan–Meier survival analysis, and Cox regression analysis. A 1:1 propensity score matching method was performed to decrease the selection bias.ResultsWe identified 1,732 patient-pairs that were completely matched. In the unmatched population, 8,198 and 1,802 patients received mastectomy only and immediate breast reconstruction, respectively. Patients who received immediate breast reconstruction had better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.880, 95% CI 0.783–0.989, P = 0.032) and overall survival (OS) (HR 0.846, 95% CI 0.758–0.943, P = 0.003) than patients who underwent mastectomy alone. However, in the matched population, there was comparable BCSS and OS between patients who received immediate breast reconstruction and mastectomy alone. Subset analysis in the matched population found that immediate breast reconstruction was associated with better BCSS (HR 0.750, 95% CI 0.614–0.917, P = 0.005) and OS (HR 0.779, 95% CI 0.644–0.942, P = 0.010) compared to patients aged <50 years who received mastectomy alone.ConclusionThere are comparable survival outcomes in LABC patients who received immediate breast reconstruction or mastectomy alone followed by PMRT. However, patients aged <50 years had a survival advantage after immediate breast reconstruction.