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BACKGROUND Geographic variations in healthcare costs have been reported for many surgical specialties. OBJECT In this study, we sought to describe national and regional costs associated with transsphenoidal pituitary surgery (TPS). METHODS Data from the Truven-MarketScan 2010-2014 was analyzed. We examined overall total, hospital/facility, physician, and out-of-pocket payments in patients undergoing TPS including technique-specific costs. Mean payments were obtained after risk-adjustment for patient- and system-level confounders and estimated differences across regions. RESULTS The estimated overall annual burden was $43 million/year in our cohort. The average overall total payment associated with TPS was $35,602.30, hospital/facility payment was $26,980.45, physician payment was $4,685.95, and out-of-pocket payment was $2,330.78. Overall total and hospital/facility costs were highest in the West and lowest in the South (both P<0.001), while physician reimbursements were highest in the North-east and lowest in the South (P<0.001). There were no differences in out-of-pocket expenses across regions. On a national level, there were significantly higher overall total and hospital/facility payments associated with endoscopic compared to microscopic procedures (both P<0.001); there were no significant differences in physician payments nor out-of-pocket expenses between techniques. There were also significant within-region cost differences in overall total, hospital/facility, and physician payments in both techniques as well as in out-of-pocket expenses associated with microsurgery. There were no significant regional differences in out-of-pocket expenses associated with endoscopic surgery. CONCLUSION Our results demonstrate significant geographical cost disparities associated with TPS. Understanding factors behind disparate costs is important for developing cost containment strategies.