Background: Autologous breast reconstruction by deep inferior epigastric perforator (DIEP) flap provides higher postoperative pain at the abdominal donor site than at the thoracic one. The authors evaluated the analgesic efficacy of ultrasound-guided transverse abdominis plane block for postoperative analgesia after immediate breast reconstruction by DIEP flap. Methods: The authors conducted an open prospective study of 30 consecutive women undergoing immediate DIEP flap breast reconstruction after modified radical mastectomy for cancer. The last 15 patients received a bilateral ultrasound-guided block with 1.5 mg/kg ropivacaine on each side after DIEP flap harvesting, under general anesthesia. All patients received postoperative acetaminophen and patient-controlled intravenous morphine and were assessed for morphine use, satisfaction with pain relief, and adverse effects. Results: Morphine requirements were significantly lower in the block group than in the control group for the 0- to 12-hour (17.7 mg versus 22.7 mg, p = 0.0047) and 12- to 24-hour (14.2 mg versus 17.4 mg, p = 0.01) intervals but not for the 24- to 36-hour (11.3 mg versus 12.2 mg, p = 0.30) and 36- to 48-hour (8.6 mg versus 8.4 mg, p = 0.65) intervals. Cumulative morphine use was lower in the block group than in the control group for the first 24 hours (32.0 mg versus 40.2 mg, p = 0.0057) and the first 48 hours (51.7 mg versus 60.5 mg, p = 0.03). There was no complication attributable to the block, with an average follow-up of 9 months. Conclusions: Bilateral ultrasound-guided transversus abdominis plane block after breast reconstruction by DIEP flap reduces the interval and cumulative morphine requirements for the first 24 and 48 hours, respectively. (Plast. Reconstr. Surg. 128: 44, 2011.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.