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Few data are available on the selective use of bilateral inferior petrosal sinus sampling (BIPSS) in the presurgical evaluation of patients with ACTH-dependent Cushing's syndrome, so we investigated whether its use only in patients without a clear adenoma on magnetic resonance imaging and/or inconsistent biochemical testing affected remission and long-term outcome after surgery in patients with Cushing's disease (CD).This was a retrospective review of patients treated for CD by one pituitary neurosurgeon at tertiary medical centers in New York City.A total of 193 consecutive adult patients who underwent initial transsphenoidal surgery (TS) for presumed CD between 1987 and 2005 were included.We examined preoperative pituitary imaging and biochemical data, results of BIPSS and surgical pathology, and outcome based on biochemical tests after initial TS and long term after subsequent therapies.Remission rate after the first TS was 80.8% overall, 79.1% in the BIPSS group (n = 105), and 83.0% in the No-BIPSS group (n = 88). Recurrences occurred in 13.5% after the first TS at a mean of 4.8 ± 3.5 yr (range, 0.7-12.4 yr) with no difference between BIPSS and No-BIPSS groups. Long-term remission was achieved after surgeries and radiotherapy in 85% (86.7% of BIPSS group, 83.0% of No-BIPSS group). CD was ultimately confirmed in all but one patient in each group.Selective use of BIPSS in the preoperative evaluation of patients with presumed CD did not lead to misdiagnosis in the No-BIPSS group or adversely affect remission rates or long-term outcome.