Postmastectomy chest wall and nodal radiation therapy decreases local recurrence and improves disease-free and overall survival. Immediate transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after mastectomy has become more common. We report on our experience of irradiating the chest wall and regional lymph nodes after a TRAM flap reconstruction and describe the acute side effects, flap viability, and cosmetic outcome. Between 1995 and 2000, 22 patients with a median age of 47 years (range 27-61 years) received chest wall radiotherapy following mastectomy and immediate pedicled TRAM flap reconstruction. The indication for radiotherapy included tumor size, involved lymph nodes, or positive margins. All patients received chemotherapy before radiotherapy and three patients also received concurrent chemotherapy. The median dose to the chest wall was 50.4 Gy in 28 fractions of 1.8 Gy using a 6 or 4 MV linear accelerator. The patients were all computed tomography (CT) planned in the treatment position. The patients were immobilized using an alpha cradle. Two tangent fields were used to deliver the dose. On alternating days, a customized bolus was applied to the chest wall that spared the central region where the subsequent nipple reconstruction would be performed. All 22 patients completed 90% of the prescribed chest wall radiotherapy dose. Sixty-six percent of the patients received treatment without any treatment breaks. Only 10% of the patients developed desquamation of the TRAM flap skin. Thirty percent developed grade II erythema of the TRAM flap. With median follow-up of 18 months, no TRAM flaps have been lost or required revision. This technique for delivery of radiotherapy to the chest wall in patients who have undergone a mastectomy and immediate TRAM flap reconstruction is well tolerated. The acute toxicity was manageable. There were no TRAM flap losses or revisions performed secondary to the radiotherapy.