The purpose of this study was to assess gender-related distinction in the performance of Cushing's disease (CD) regarding clinical features, radiological findings, neurological and endocrine status, surgical outcome, and quality of life in Han Chinese. A retrospective study was conducted on 87 patients treated by trans-sphenoidal surgery, between 2006 and 2011, at a single treatment center in Shandong Provincial Hospital, China. Features of CD were compared and quality of life was analyzed between genders. The female-to-male ratio was 2.78: 1. Results showed that men have a younger age of diagnosis (P<0.001), a larger adenoma diameter (P<0.001), and a higher invasion rate (P=0.032) and apoplexy rate (P=0.04) than women. To be specific, compared with women, men are more prone to suffering from osteoporosis, hypokalemia, sexual dysfunction, and hypertension (P<0.05), have significantly higher preoperative and postoperative (six months after surgery) cortisol levels (P<0.001, P=0.003) and a higher recurrence rate (30.43% vs. 7.81%; P=0.028). No significant differences were seen in the CushingQoL scores between genders. Therefore, male patients with CD need more careful and long-term follow-up than female patients.