ObjectiveTo understand the transition from microscopic surgery (MS) to endoscopic surgery (ES) on the pituitary across the United States, we assessed a single institution practicing both procedures to discern advantages and disadvantages for each. Patients and MethodsRetrospective institutional chart review of 534 patients in a large practice over a 6-year period (January 1, 2014, to December 31, 2019) comparing a single MS neurosurgeon with a single ES neurosurgeon operating on the same days. ResultsIn this series, 14% (n=75) of patients had a prior operation, there were no carotid artery injuries, the overall risk for a postoperative infection was 0.4% (n=2), and risk for a postoperative cerebrospinal fluid leak requiring treatment was 2.0% (n=11). Mean ± SD hospital stay was 1.3±0.04 days; readmission for any reason within 30 days occurred in 3.4% (n=18) of patients. The mean volumetric resection for MS was 86.9%±1.7% and for ES was 91.7%±1.3% (P=.03). There was a higher rate of notable events (P=.015) with MS, but MS had 16% lower cost and operative times were 48 minutes shorter than for ES (83±7 vs 131±6 minutes). The ES required substantially fewer postoperative secondary treatments such as radiation therapy (P=.003). ConclusionPituitary surgery is a very safe and effective procedure regardless of technique. The MS has shorter operative times and overall lower cost. The ES results in increased volumetric resection and fewer secondary treatments. Both techniques can be valuable to a large practice, and understanding these niches is important when selecting optimal approaches to pituitary surgery for a given patient.