Transsphenoidal surgery (TSS) harbors a potential for hypopituitarism, cerebrospinal fluid (CSF) leaks, and other complications. We utilized the Nationwide Inpatient Sample Database (NIS) to compare inpatient complication rates between Cushing's disease (CD) and non-Cushing's disease (NCD) patients undergoing TSS.Inpatient hospitalization data for 960 CD and 12 110 NCD patients who underwent TSS between 2002 and 2010 were accessed. Demographic information, outcomes, and complication rates were evaluated.Patients with CD had a female predilection (81.7%) and were younger (40.5 ± 14.4 years) than NCD patients (47.8% female; 52.1 ± 16.3 years) (P < .001). Length of stay and total charges did not differ between groups. Patients with CD had significantly greater postoperative diabetes insipidus rates (14.0% vs 9.6%, P < .001) and urinary/renal complications (1.7% vs 0.9%, P = .027). After adjusting for possible confounders, the relationship between urinary/renal complications and CD status strengthened. There was no difference in rates of CSF leak and iatrogenic pituitary disorders overall.No differences were noted in the rate of early CSF leaks between postoperative TSS CD and NCD patients. Postoperative diabetes insipidus did not significantly differ between groups after adjusting for confounders. Only odds of urinary/renal complications in CD patients was significant after adjustment.