The prevalence of anastomotic failure resulting in return to the operating room and flap necrosis after microvascular breast reconstruction ranges from 1 to 5 percent. The purpose of this study was to review a set of factors that may be associated with this occurrence. Microvascular reconstruction of the breast was performed in 198 women from January of 1998 to July of 2002. The mean age for all women was 47.7 years. There were 158 unilateral and 41 bilateral reconstructions, for a total of 240 flaps. The specific flaps included the free transverse rectus abdominis musculocutaneous flap (n = 176), the deep inferior epigastric perforator flap (n = 58), and the superior gluteal artery perforator flap (n = 6). Upon recognition of anastomotic failure, women were immediately returned to the operating room. Factors that were considered relevant to anastomotic failure included the choice of recipient vessel, timing of reconstruction, previous chest wall radiation therapy, previous axillary lymph node dissection, tobacco use, diabetes mellitus, patient age, and hematoma. Patient follow-up ranged from 5 to 59 months. Descriptive statistics, Fisher's exact test, and exact logistic regression were used for analyses and to summarize data. Of the 240 flaps, return to the operating room was necessary for 20 (8.3 percent), total necrosis occurred in nine (3.8 percent), and the rate of flap salvage was 55 percent (11 of 20 flaps). Venous occlusion was responsible for 16 of the 20 returns and eight of the nine failures. Statistical analysis demonstrated that both return to the operating room and flap necrosis were significantly associated with venous occlusion, delayed reconstruction, and hematoma. Previous lymph node dissection and previous radiation therapy had only a weak association with return to the operating room. The results of this study demonstrate that venous occlusion is responsible for return to the operating room and flap necrosis in the majority of cases. Age, tobacco use, choice of recipient vessel, and diabetes mellitus were not associated with anastomotic failure. The significance of delayed reconstruction may be related to its frequent association with previous lymph node dissection and/or radiation therapy resulting in perivascular fibrosis.