Loss of a breast free flap is a relatively rare but catastrophic occurrence. Our study aims to identify risk factors for flap loss and to assess whether different salvage techniques affect flap salvage. We performed a retrospective review of all breast free flaps performed at a single institution from 2000 to 2010. Overall, 2138 flaps were performed in 1608 patients (unilateral, 1120 and bilateral, 488) with 44 flap losses (2.1%). Age, body mass index, smoking, radiation, chemotherapy, and surgeon experience did not affect flap loss. Abdominal flaps based on a single perforator were at significantly higher risk for flap loss compared with flaps based on multiple perforators (P = 0.0007). Subgroup analysis of the subset of 166 compromised free flaps (flaps requiring a return to the operating room, an intraoperative anastomotic revision, or loss/partial loss of a free flap) demonstrated deep inferior epigastric perforator, and other flaps (superficial inferior epigastric artery and superior gluteal artery perforator) were significantly associated with flap loss [odds ratio (OR) 5.20; P = 0.03 and OR 6.91; P = 0.0004, respectively] compared with transverse rectus abdominis myocutaneous and muscle-sparing transverse rectus abdominis myocutaneous flaps. Although an intraoperative complication was not associated with a flap loss, the need for a reoperation was strongly predictive (P < 0.0001). Flap salvage was the highest within the first 24 hours (83.7%) and significantly less between days 1 and 3 (38.6%; P < 0.0001) and beyond 4 days (29.4%; P < 0.0001). Longer ischemia time was significantly associated with flap loss (P = 0.04). Salvage techniques (aspirin, heparinzation, thrombectomy, and thrombolytic) had no impact on flap salvage rates. Heparinization and thrombolytics were associated with higher loss rates (OR 3.40; P = 0.003 and OR 10.36; P < 0.0001, respectively). Free flap loss following breast reconstruction is multifactorial with higher losses in superficial inferior epigastric artery and gluteal flaps, single-perforator abdominal flaps, and longer ischemia times. Salvage rates are most successful within the first 24 hours, and the use of heparinization, aspirin, and thrombolytics does not improve salvage rates.