Abstract BACKGROUND Accurate assessment of the need for glucocorticoid therapy is essential after transsphenoidal surgery (TSS) for pituitary tumors. Agreement on the best test to use in the early postoperative setting is lacking. OBJECTIVE To examine recovery room (RR) cortisol as a predictor of long-term need for glucocorticoids. METHODS We conducted a retrospective cohort study of 149 patients who underwent TSS for pituitary tumors between January 2007 and December 2014. Pathological tumor diagnoses were confirmed. Endocrinologists assessed the need for glucocorticoid supplementation within 6 to 8 wk after TSS. We extracted data on preoperative, RR, and day 1 to 3 post-TSS morning serum cortisol (MSC). We reported areas under the receiver operating characteristic curve (AUC) and diagnostic measures for different cortisol measures. We also conducted a logistic regression to identify the most predictive variables. RESULTS Eighteen patients required glucocorticoid supplementation at follow-up. RR cortisol was the most accurate measurement in the early postoperative period (AUC [95% confidence interval (CI)], .92 [.85-.99]; P < .001), followed by day 1, 2, and 3 post-TSS MSC, respectively. A threshold RR cortisol of 744.0 nmol/L (26.97 μg/dL) had 90.9% sensitivity and 73.7% specificity for detecting patients in the hypocortisolism group, while 757.5 nmol/L (27.46 μg/dL) had 100% and 70.0%, respectively. The logistic regression identified RR cortisol as the sole significant predictor (odds ratio [CI], .36[.18-.71] for every 100 nmol/L increase; P = .0033). CONCLUSION The RR cortisol is accurate in predicting long-term glucocorticoid supplementation and may be the best early postoperative measure. Future larger studies should validate these findings and derive optimal RR cortisol threshold values.