Introduction: Cushing disease is a rare problem that usually has an important effect on the quality of life (QoL). Objective: This survey aimed to evaluate patients’ QoL and determine predictors of improving QoL scores in patients. Materials and Methods: In this before-after study, basic characteristics were collected from 56 patients with Cushing disease who underwent endoscopic transsphenoidal surgery, and their QoL score during one year was assessed. Finally, predictor factors of QoL score improvement were identified. To compare the QoL scores before, 6 months, and 12 months after surgery, repeated measures ANOVA and for determining predictors of QoL score improvement, multivariable logistic regression analysis was used. P<0.05 was considered significant in all tests. Results: The mean±SD age of the samples was 33.92±12.82 years, and 43 (76.8%) were female. In all 56 patients who underwent endoscopic transsphenoidal surgery, the QoL score significantly improved. In multivariable logistic regression analysis, weight loss (OR= 1.2, 95% CI; 1.01-6.5, P=0.01), no fatigue (OR= 2.1, 95%CI; 1.6-8.3, P=0.009), no decreased libido (OR= 1.5, 95% CI; 1.2-10.62, P=0.01), no gonadal axis disorder (OR=2.2, 95% CI; 1.07-4.06, P=0.01) and post-operation no thyroid axis disorder (OR=2.5, 95% CI; 1.8-5.7, P=0.01) were predictors for more QoL score improvement. Conclusion: According to the results of this study, many factors can affect the quality of life in patients with Cushing disease. Therefore, support groups should include the cooperation of physicians and psychologists, provision of health services, and social support to improve the QoL of patients.