Aim:Surgical resection is a critical tool in sellar lesion management. Both transnasal transsphenoidal (TNTS) and transcranial (TC) approaches are viable options, although each possess relative advantages and limitations. We present a national database analysis comparing these techniques.Material and Methods:We analyzed the National Surgical Quality Improvement Program (NSQIP) database by TNTS and TC CPT codes from 2014-2018. Outcome measures included periprocedural complications, surgical complications, reoperation within 30 days, readmission, and death. Statistical comparisons were made using Wilcoxon rank-sum test in STATA.Results:A total of 488 procedures were identified (232 TC; 256 TNTS). Baseline demographics were comparable between groups. Patients undergoing craniotomy were more likely to have DVT or PE (8 vs 2 patients, p=0.042) and stroke (11 vs 0 patients, p<0.001). TC approach was associated with longer hospital length-of-stay (6.1 vs 4.2 days, p<0.001), 30-day readmission (15.8% vs 7.1%), and death (2.6% vs 0.4%, p=0.042). Craniotomy was more likely to be performed in nonelective cases (26.3% vs 12.6%, p<0.001), however the difference in complication rates was driven by elective cases.Conclusion:We found that the TC approach to the sella was associated with higher rates of complications and greater mortality than the TNTS approach. The TC approach was also more likely to be performed in nonelective cases, but the difference in morbidity and mortality was driven by elective cases. Further study is warranted to identify lesion characteristics that may influence choice of approach and outcomes.