OBJECTIVE Following successful transsphenoidal surgery in patients with growth hormone (GH)-secreting pituitary adenomas, a characteristic fluid diuresis has been described. In this paper the authors aimed to further analyze the degree of fluid diuresis as it relates to postoperative GH levels. METHODS Between 2000 and 2008, 85 patients underwent transsphenoidal surgery for a GH-secreting adenoma at the USC University Hospital. A retrospective chart review was conducted. Postoperative fluid intake, output, and balance within 48 hours following surgery, as well as endocrinological data were recorded and analyzed. Patients with postoperative diabetes insipidus and those with insufficient data were excluded from analysis. RESULTS Seventy-one patients were included in the analysis. The mean age was 46 years (range 16-74 years). There were 36 males (51%) and 35 females (49%). Patients with negative fluid balances at 48 hours after surgery were more than twice as likely to have a GH level of < 1.5 ng/ml (55 vs 25%, p = 0.023). At 48 hours after surgery, patients with a negative overall fluid balance had a significantly lower median GH level than those with a positive overall fluid balance (1.3 vs 2.4 ng/ml, p = 0.039). This difference was even more pronounced in patients with microadenomas and a negative overall fluid balance. By 48 hours following surgery, patients with postoperative Day 1 GH levels < 1.5 ng/ml had, on average, experienced diuresis of fluid > 1.1 L (median 1.5 L) more than patients with GH levels > 1.5 ng/ml. CONCLUSIONS Successful resection of GH-secreting adenomas is associated with a more pronounced fluid diuresis and negative overall fluid balance within 48 hours following transsphenoidal surgery. Patients with a negative fluid balance by postoperative Day 2 have a higher likelihood of having significantly reduced postoperative GH levels that may correlate with long-term surgical remission.