Study Design. Retrospective cohort analysis. Objective. To investigate the safety profile of outpatient versus inpatient single-level and multiple-level cervical disk replacement (CDR) by analyzing one-and two-year surgical outcomes and 90-day medical complications using a large patient database. Summary of Background Data. CDR is becoming a more desirable option for patients undergoing cervical spine procedures. Unlike anterior cervical diskectomy and fusion, CDR is motionpreserving and has been shown to reduce rates of adjacent segment disease. Current literature investigating outpatient versus inpatient CDR has shown a similar safety profile among the two cohorts. However, most of these studies have relatively small sample sizes with short-term follow-up. Materials and Methods. A retrospective cohort study was done using the PearlDiver patient database between 2010 and 2019. Patients who underwent single-level and multiple-level CDR with a follow-up of at least two years were identified. Patients within each procedure cohort were subdivided into an outpatient and an inpatient group. Univariate and multivariable analyses were performed. Results. In total, 2294 patients underwent single-level CDR of which 506 patients underwent outpatient CDR and 1788 underwent inpatient CDR. In total, 236 patients underwent multiple-level CDR of which 49 patients underwent outpatient CDR and 187 underwent inpatient CDR. In the single-level CDR cohort, patients undergoing outpatient CDR were found to have lesser odds of a decompressive laminectomy at one year following the initial procedure (odds ratio = 0.471; 95% confidence interval. 0.205-0.945; P = 0.05). No significant differences in one-and two-year surgical complications, or 90-day postoperative complications, were found on multivariate analysis of outpatient versus inpatient multiple-level CDR. Conclusion. Our study found that performing single-level and multiple-level CDR on an outpatient basis has a similar safety profile to patients who underwent these procedures in an inpatient setting.