Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.