Immediate or delayed reconstruction using implants or autologous tissue transfer is increasingly offered to women undergoing mastectomy for breast cancer. Some patients require radiotherapy for prevention of local/regional relapse, and some for post-surgical local/regional recurrence. Others with augmented breasts may opt for conservative surgery and irradiation. At Washington University, 70 breast cancers were irradiated in 66 patients following mastectomy with reconstruction (N = 61) or wide local excision of an augmented breast (N = 5). Two patients elected to have a second reconstruction after an unsatisfactory initial result. Thus, 72 breasts were evaluated after radiotherapy for tumor control, complications, cosmesis, and patient satisfaction. Locoregional failure occurred in only five patients, one following adjuvant radiotherapy after mastectomy with reconstruction and four following radiotherapy for recurrent breast cancer within a reconstructed breast. Grade 2 or 3 complications occurred in 34 patients (51%). The complication rate was highest in autologous tissue transfer reconstructions. Cosmetic results were evaluated good/excellent in 49% by physicians and 67% by patients. Immediate reconstructions had fewer good/excellent physician evaluations (32%) compared with reconstructions performed at least 6 weeks after radiotherapy (55%). Transverse rectus abdominis flaps had the best cosmesis scores, followed by permanent silicone prostheses, tissue expanders, latissimus dorsi, and gluteal flaps. Only 48% of patients would choose to have the same reconstructive procedure again. Phantom interface dosimetry with a parallel plate chamber and TLD measurements was performed. Radiotherapy and reconstruction are not incompatible, but careful consideration of their relative timing and technique appear to be important in optimizing cosmesis while minimizing complications.