Transsphenoidal surgery (TSS) is the first-line treatment of patients with Cushing's disease (CD). However, biochemical remission rates after TSS for CD vary from 59 to 95%, and the predictors of surgical outcomes remain unclear. The aim of this study was to identify the predictors of early outcomes in patients with CD treated with TSS.The clinical features and outcomes of CD patients who underwent TSS between February 2000 and September 2019 at the Peking Union Medical College Hospital were collected from medical records and analyzed. Uni- and multivariate odds ratio (OR) analyses were performed to identify the predictors of early outcomes in patients with CD.A total of 1,045 patients were included. The median age at TSS was 34.0 years (IQR 26.0-45.0), with a female:male ratio of 4.2:1 (844/201). The median duration of symptoms was 46.0 months (IQR 24.0-72.0). After surgery, the overall postoperative immediate remission rate was 73.3%, and 26.7% of patients had persistent hypercortisolism. Univariate analysis demonstrated that the number of operations was correlated with a lower immediate remission rate (OR 0.393, 95% CI 0.266-0.580, p = 0.000), as was tumor size (OR 0.462, 95% CI 0.334-0.639, p = 0.000), the duration of disease (OR 0.996, 95% CI 0.993-0.999, p = 0.003), and preoperative ACTH concentration (0.998, 95% CI 0.996-0.999, p = 0.003). Cavernous sinus invasion has also been identified as an important factor associated with a lower immediate remission rate (OR 0.275, 95% CI 0.166-0.456, p = 0.000). No correlations were detected between the immediate outcomes and age, gender, BMI, the combination of a low- and high-dose dexamethasone suppression test, preoperative morning serum cortisol level, or 24-h urinary free cortisol level (all p > 0.05). The results of multivariate analysis were similar to those of univariate analysis. Preoperative ACTH ≤67.35 ng/L predicted remission with 60.9% sensitivity and 49.5% specificity (AUC 0.553; p = 0.008). A cutoff of ≤64.5 months for disease duration predicted immediate remission with 40.5% sensitivity and 71.0% specificity (AUC 0.552; p = 0.01).Early outcomes of TSS in CD patients can be predicted by factors including the number of operations, duration of disease, tumor invasion, tumor size, and preoperative ACTH concentration. These predictors can be used to improve the perioperative management of CD patients.© 2020 S. Karger AG, Basel.