Chest wall irradiation is becoming increasingly common for mastectomy patients who have opted for immediate breast reconstruction with tissue expanders and implants. The optimal approach for such patients has not yet been defined. This study assesses the outcomes of a reconstruction protocol for patients who require irradiation after tissue expander/implant reconstruction. The charts of all patients who underwent immediate tissue expander/implant reconstruction at Memorial Sloan-Kettering Cancer Center between January of 1995 and June of 2001 and who had not previously undergone irradiation were retrospectively reviewed. A subgroup of patients who required chest wall irradiation after mastectomy and reconstruction was identified. Those patients were treated according to the following treatment algorithm: (1) reconstruction with tissue expander placement at the time of mastectomy, (2) tissue expansion during postoperative chemotherapy, (3) exchange of the tissue expander for a permanent implant approximately 4 weeks after the completion of chemotherapy, and (4) chest wall irradiation beginning 4 weeks after the exchange. All irradiated patients with at least 1 year of follow-up monitoring after the completion of radiotherapy were evaluated with respect to aesthetic outcomes, capsular contracture, and patient satisfaction. A control group of nonirradiated patients was randomly selected from the cohort of patients treated during the study period. During the 5-year study period, a total of 687 patients underwent immediate reconstruction with tissue expanders. Eighty-one patients underwent postoperative irradiation after placement of the final implant. A total of 68 patients who received postoperative chest wall irradiation underwent at least 1 year of follow-up monitoring after the completion of radiotherapy, with a mean follow-up period of 34 months. Seventy-five nonirradiated patients were evaluated as a control group. Overall, 68 percent of the irradiated patients developed capsular contracture, compared with 40 percent in the nonirradiated group (p = 0.025). Eighty percent of the irradiated patients demonstrated acceptable (good to excellent) aesthetic results, compared with 88 percent in the nonirradiated group (p = not significant). Sixty-seven percent of the irradiated patients were satisfied with their reconstructions, compared with 88 percent of the nonirradiated patients (p = 0.004). Seventy-two percent of the irradiated patients stated that they would choose the same form of reconstruction again, compared with 85 percent of the nonirradiated patients. The results of this study suggest that tissue expander/implant reconstruction is an acceptable surgical option even when followed by postoperative radiotherapy and should be considered in the reconstruction algorithm for all patients, particularly those who may not be candidates for autogenous reconstruction.