ALIF (anterior lumbar interbody fusion) and other spinal fusion surgeries are among the most common orthopaedic procedures requiring blood transfusions. However, blood transfusions have been associated with various complications, including adverse reactions and infections. The present study aims to identify independent risk factors for blood transfusions in patients undergoing single-level ALIF specifically to better identify high risk patients and optimize perioperative management. All patients who had undergone single-level ALIF patients for the treatment of degenerative spinal conditions, excluding traumatic, pathologic, and infectious etiologies, were identified by querying a multi-institutional surgical registry from 2005 to 2018. Multi-level fusions, PLIF/TLIF, and posterior procedures were also excluded. Mann-Whitney-U-Tests were used to analyze continuous variables, while Fisher's-Exact-Tests/Bonferroni-Corrected-Tests were used for categorical variables. Multivariate logistic regression analysis with alternating backward stepwise elimination and forward entry was implemented to identify significant predictors for blood transfusions within 72 hours after incision. The predicted probabilities were used in post-regression diagnostics to generate a Receiver Operating Characteristic (ROC) curve to assess model performance. 4,792 single-level ALIF patients met inclusion criteria - 183 (3.82%) had received blood transfusions within 72 hours after incision and 4,609 (96.18%) had not. Age ≥60 years (OR 1.954, p<0.001), preoperative transfusions (OR 33.758, p=0.023), extended operative times (≥197.0 minutes; 75th percentile) (OR 4.645, p<0.001), ASA≥3 (OR 1.395, p<0.001) and preoperative hematocrit levels (Hct) 30.00-37.99 (OR 1.562, p=0.016) and Hct <30.00 (OR 6.334, p<0.001) were shown to be significant independent risk factors for perioperative blood transfusions. The area under the ROC curve (AUROC; C-statistic) was 0.759 (p<0.001), indicating relatively strong discriminatory ability/predictability of the final model. Several independent risk factors including age ≥60 years, preoperative blood transfusions and extended operative times increased risk for blood transfusion following single-level ALIF. The present study aims to help surgeons identify high-risk patients to better communicate postoperative expectations and optimize patients to reduce the risk of transfusions and secondary complications. .