Patients with node positive or locally advanced breast cancer desiring deep inferior epigastric perforator (DIEP) flap reconstruction frequently require postmastectomy radiation therapy (PMRT). To avoid the deleterious effects of PMRT, surgeons will often delay reconstruction until after PMRT is complete. Drawbacks to this approach include additional surgery, recuperation, cost, and an extended reconstructive process. Even if a tissue expander is used to preserve the skin envelope during irradiation, the post-PMRT breast pocket is often distorted or constricted necessitating some skin replacement, resulting in a compromised aesthetic outcome. Therefore, a systematic approach to mitigate the deleterious effects of PMRT was developed, and primary DIEP flap reconstruction was offered to patients requiring PMRT. This study evaluates the outcome of this approach in a cohort of patients undergoing immediate bilateral DIEP flap reconstruction with unilateral PMRT, allowing comparison between irradiated and nonirradiated flaps. One hundred twenty-five patients who underwent immediate DIEP reconstruction between 2009 and 2011 were identified. Eleven consecutive patients had bilateral DIEP reconstructions by a single surgeon and received unilateral PMRT. Preoperative, intraoperative, and postoperative steps were taken in all patients to ensure flap vascularity, prevent uncontrolled contracture, and limit radiation damage to the breast mound. Results were documented photographically and the irradiated and nonirradiated breasts were compared. The complication rates, incidence of clinically significant fat necrosis, and need for reoperation were examined. Median follow-up was 18 months (range, 8-21 months). Complications were minor and did not require readmission to the hospital or reoperation. There was no incidence of clinically significant fat necrosis in either the irradiated or nonirradiated DIEP flaps. Four operative revisions for breast symmetry were required in 3 of 11 patients. Aesthetic outcomes were deemed satisfactory in all patients. Primary reconstruction with DIEP flaps can be performed successfully in patients who require PMRT if steps are taken to ensure flap vascularity, minimize fibrosis, optimize contour, and modulate radiation dosing.