Abstract Background Context Blood transfusions in spine surgery are shown to be associated with increased patient morbidity. The association between transfusion performed using a liberal hemoglobin trigger—defined as an intraoperative hemoglobin level of ≥10 g/dL, a postoperative level of ≥8 g/dL, or a whole hospital nadir between 8-10 g/dL—and perioperative morbidity and cost in spine surgery patients is unknown and thus was investigated in this study. Purpose To describe the perioperative outcomes and economic cost associated with liberal hemoglobin trigger transfusion among spine surgery patients. Study Design/Setting Retrospective study. Patient Sample The surgical billing database at our institution was queried for inpatients discharged between 2008 and 2015 after the following procedures: atlantoaxial fusion, anterior cervical fusion, posterior cervical fusion, anterior lumbar fusion, posterior lumbar fusion, lateral lumbar fusion, other procedures, and tumor-related surgeries. In total, 6931 patients were included for analysis. Outcome Measures The primary outcome was composite morbidity which was comprised of: (1) infection (sepsis, surgical-site infection, Clostridium dificile, or drug-resistant infection), (2) thrombotic event (pulmonary embolus, deep venous thrombosis, or disseminated intravascular coagulation), (3) kidney injury, (4) respiratory event, and/or (5) ischemic event (transient ischemic attack, myocardial infarction, or cerebrovascular accident). Methods Data on intraoperative transfusion were obtained from an automated prospectively collected anesthesia data management system. Data on postoperative hospital transfusion was obtained through a Web-based intelligence portal. Based on previous research, we analyzed the data using three definitions of a liberal transfusion trigger in patients who received an RBC transfusion: a liberal intraoperative Hb trigger as a nadir Hb level of 10 g/dL or greater, a liberal postoperative Hb trigger as a nadir Hb level of 8 g/dL or greater, or a whole hospital nadir Hb level of 8-10 g/dL. Variables analyzed included in-hospital morbidity, mortality, length of stay, and total costs associated with a liberal transfusion strategy. Results Among patients with a whole hospital stay nadir hemoglobin between 8 to 10 g/dL, transfused patients demonstrated a longer in-hospital stay (median IQR, 6 5-9 vs. 4 3-6 days; P<0.0001) and a higher perioperative morbidity (n=145, 11.5% vs. n=74, 6.1%; P<0.0001) than those not transfused. Even after adjusting for age, gender, race, ASA class, CCI score, estimated blood loss, baseline hemoglobin value, number of operated levels, and surgery type, logistic regression analysis revealed that patients with a nadir hemoglobin of 8-10 g/dL who were transfused had an independently higher risk of perioperative morbidity (odds ratio OR = 2.12; 95% confidence interval CI, 1.24-3.64; P=0.006). Estimated additional costs associated with liberal trigger use, defined as a transfusion occurring in patients with a whole hospital stay nadir Hb of 8-10 g/dL, ranged from $202,675 to $700,151 annually. Conclusions Transfusion using a liberal trigger is associated with increased morbidity, even after controlling for possible confounders. Our results suggest that modification of transfusion practice may be a potential area for improving patient outcomes and reducing costs.