National databases are increasingly being used for research in spine surgery; however, one limitation of such databases that has received sparse mention is the frequency of missing data. Studies using these databases often do not emphasize the percentage of missing data for each variable used and do not specify how patients with missing data are incorporated into analyses. This study uses the American College of Surgeons National SurgicalQuality Improvement Program (ACS-NSQIP) database to examine whether different treatments of missing data can influence the results of spine studies. (1) What is the frequency of missing data fields for demographics, medical comorbidities, preoperative laboratory values, operating room times, and length of stay recorded in ACS-NSQIP? (2) Using three common approaches to handling missing data, how frequently do those approaches agree in terms of finding particular variables to be associated with adverse events? (3) Do different approaches to handling missing data influence the outcomes and effect sizes of an analysis testing for an association with these variables with occurrence of adverse events? Patients who underwent spine surgery between 2005 and 2013 were identified from the ACS-NSQIP database. A total of 88,471 patients undergoing spine surgery were identified. The most common procedures were anterior cervical discectomy and fusion, lumbar decompression, and lumbar fusion. Demographics, comorbidities, and perioperative laboratory values were tabulated for each patient, and the percent of missing data was noted for each variable. These variables were tested for an association with "any adverse event" using three separate multivariate regressions that used the most common treatments for missing data. In the first regression, patients with any missing data were excluded. In the second regression, missing data were treated as a negative or "reference" value; for continuous variables, the mean of each variable's reference range was computed and imputed. In the third regression, any variables with >10% rate of missing data were removed from the regression; among variables with ≤10% missing data, individual cases with missing values were excluded. The results of these regressions were compared to determine how the different treatments of missing data could affect the results of spine studies using the ACS-NSQIP database. Of the 88,471 patients, as many as 4441 (5%) had missing elements among demographic data, 69,184 (72%) among comorbidities, 70,892 (80%) among preoperative laboratory values, and 56,551 (64%) among operating room times. Considering the three different treatments of missing data, we found different risk factors for adverse events. Of 44 risk factors found to be associated with adverse events in any analysis, only 15 (34%) of these risk factors were common among the three regressions. The second treatment of missing data (assuming "normal" value) found the most risk factors (40) to be associated with any adverse event, whereas the first treatment (deleting patients with missing data) found the fewest associations at 20. Among the risk factors associated with any adverse event, the 10 with the greatest effect size (odds ratio) by each regression were ranked. Of the 15 variables in the top 10 for any regression, six of these were common among all three lists. Differing treatments of missing data can influence the results of spine studies using the ACS-NSQIP. The current study highlights the importance of considering how such missing data are handled. Until there are better guidelines on the best approaches to handle missing data, investigators should report how missing data were handled to increase the quality and transparency of orthopaedic database research. Readers of large database studies should note whether handling of missing data was addressed and consider potential bias with high rates or unspecified or weak methods for handling missing data.