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Study Design Case-control study; Level of evidence, 3. Objective Anterior cervical discectomy and fusion (ACDF) is one of the most common procedures for cervical diseases often with reliable outcomes. However, morbidity rates can be as high as 19.3% so appropriate patient selection and risk stratification is imperative. Our modified frailty index (MFI) predicts postoperative complications after other orthopaedic procedures. We hypothesized that this index would predict complications in a large cohort of ACDF patients. Methods We reviewed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, including patients who underwent ACDF from 2015-2020. An 8-item MFI score was calculated for each patient. We recorded 30-days postoperative complications, readmission, and reoperation rates, adjusting for baseline features using standard multivariate regression. This project was approved of by the University of Texas Health Science Center Institutional Review Board and an IRB exception was granted. Results We identified 17 662 ACDF cases. Patients with MFI of 5 or greater had a 37.53 times increased odds of incurring postoperative complications compared to patients with MFI of 0 ( P < .001) even when age, sex, race, and ethnicity were controlled for. Specifically, life-threatening Clavien-Dindo IV complications, as well as wound, cardiac, renal, and pulmonary complications were significantly increased in patients with an MFI of 5 or greater. Also, as MFI increased from 1-2 to 3-4 to 5 or greater, the odds of readmission increased from 1.36 to 2.31 to 5.42 times ( P < .001) and odds of reoperation from 1.19 ( P = .185) to 2.3 to 6.54 times ( P < .001). Frailty was still associated with increased complications, readmission, and reoperation after controlling for demographic data, including age, as well as operative time and length of stay. Conclusion Frailty is highly predictive of postoperative complications, readmission, and reoperation following ACDF. Employing a simple frailty evaluation can guide surgical decision-making and patient counseling for cervical disease.