BACKGROUNDOver the past decade, the prevalence of obesity has risen in the United States, in parallel with the demand for anterior cervical discectomy with fusion (ACDF). Prior studies have evaluated the role of obesity classes in cervical spine surgery in smaller patient populations. We aimed to evaluate any potential correlation to a national population sample by utilizing a large multicenter database. PURPOSEThe purpose of this study was to analyze obesity level's influence on perioperative complication rates in patients undergoing ACDF. STUDY DESIGN/SETTINGA retrospective cohort, large multicenter database study. PATIENT SAMPLEThe American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify patients who had undergone an elective ACDF procedure between 2011 and 2020 using Current Procedural Terminology (CPT) code 22551. OUTCOME MEASURESMedical and surgical complications within thirty days of operation. METHODSPatients were categorized into four BMI groups: nonobese (BMI 18.5−29.9 kg/m2), obese class I (BMI 30−34.9 kg/m2), obese class II (BMI 35−39.9 kg/m2), and obese class III (BMI ≥40 kg/m2). A univariate analysis conducted for demographic variables and preoperative comorbidities identified age, sex, race, smoking status, hypertension requiring medication, diabetes, history of congestive heart failure, history of bleeding disorder, and chronic obstructive pulmonary disease as risk factors. Chi-square test was used to compare incidence of complications among groups. A multivariable logistic regression analysis was subsequently performed to adjust for these preoperative risk factors and compare obesity classes I-III to nonobese patients. RESULTSAbout 64,718 patients were identified of whom 33,365 were nonobese, 17,190 were obese class I, 8,608 were obese class II, and 5,555 were obese class III. Obese classes I-III patients had a higher incidence of surgical site infections (0. 33%, 0.36%, 0.41%, vs. 0.24%, p=.039) and pulmonary embolism (PE) (0.25%, 0.31, 0.29 vs. 0.15%, p=.003). Obese classes I-III had a lower incidence of blood transfusion (0.23%, 0.17%, 0.27% vs. 0.4%, p<.001) obese class I, obese class II, and obese class III independently increased the risk for PE (OR: 1.716, 95% CI (1.129−2.599); OR: 2.213, 95% CI (1.349−3.559); OR: 2.207, 95% CI (1.190--3.892), respectively). CONCLUSIONSRisk for postoperative PEs after an ACDF was significantly higher for obese classes I-III compared to nonobese patients. These findings may further support the use of additional prophylaxis measures and precaution in the perioperative setting.