Background Immediate breast reconstruction after mastectomy and delayed breast reconstruction with post-supplementary treatment are the two types of breast reconstruction currently performed when treating breast cancer. Post-mastectomy radiation therapy (PMRT) not only reduces local recurrence but also improves overall survival. However, the complications and survival rates associated with PMRT need to be clear when determining the timing of breast reconstruction. Accordingly, we investigated the optimal timing of breast reconstruction by observing patients who underwent mastectomy followed by PMRT, based on their overall health and aesthetic satisfaction. Methods We retrospectively reviewed 21 patients who underwent breast reconstruction with PMRT between November 2004 and November 2010. We collected data regarding the various methods of mastectomy, and the modality of adjuvant therapy, such as chemotherapy, hormone therapy, and radiotherapy. Telephone interviews were conducted to study the general and aesthetic satisfaction. Results Patients who received PMRT after breast reconstruction showed a greater complication rate than those undergoing breast reconstruction after PMRT (P=0.02). Aesthetic satisfaction was significantly higher in the groups undergoing breast reconstruction after PMRT (P=0.03). Patients who underwent breast reconstruction before PMRT developed complications more frequently, but they expressed greater aesthetic satisfaction with the treatment. Conclusions It is recommended that the complication rates and aesthetic satisfaction after breast reconstruction be carefully considered when determining the optimal timing for radiotherapy.