Objective To explore the sex difference in clinical manifestations, echocardiographic features and prognosis of patients with bicuspid aortic valve (BAV) combined with moderate to severe aortic stenosis (AS). Methods The clinical data and echocardiographic follow-up parameters of patients diagnosed with BAV combined with moderate to severe AS at Zhongshan Hospital, Fudan University, from July 30, 2010 to August 1, 2015 were retrospectively collected. The composite endpoint was defined as all-cause mortality or surgical intervention. Kaplan-Meier survival curve and log-rank test were used to compare the risk of composite endpoint events between male and female patients, and Cox regression models were used to analyze independent risk factors for composite endpoint events. Results A total of 144 patients were included, with 69 males and 75 females, and a median age of 60 years. Compared to males, female patients were younger (58[46, 65] years vs 61[54, 67] years, P＝0.046), had a lower proportion of aortic valve calcification (61.1% vs 81.1%, P＝0.009), and a higher peak transvalvular pressure gradient (72[59, 88] mmHg vs 63[55, 72] mmHg, P＝0.002). In terms of left ventricular remodeling types, the proportion of concentric remodeling was higher in females than in males (36.0% vs 15.9%, P＝0.006), while the proportion of eccentric hypertrophy was lower in females than in males (10.7% vs 29.0%, P＝0.006). The proportion of female patients classified as New York Heart Association (NYHA) functional class Ⅲ-Ⅳ was higher than that of males (45.3% vs 17.4%, P＜0.001), and left ventricular ejection fraction was higher in females (68%[65%, 72%] vs 65%[60%, 70%], P＝0.003). With a median follow-up of 49 months, Kaplan-Meier survival analysis showed that the risk of composite endpoint events was higher in females than in males (P＜0.001). Independent risk factors for composite endpoint events included female (HR＝1.74, 95%CI 1.02-2.96, P＝0.042), severe AS (HR＝1.99, 95%CI 1.18-3.36, P＝0.010), and NYHA functional class Ⅲ-Ⅳ (HR＝2.08, 95% CI 1.24-3.47, P＝0.005). Conclusions Sex significantly affects the clinical manifestations, echocardiographic characteristics, and prognosis of patients with BAV combined with moderate to severe AS, suggesting that sex-specific echocardiographic assessment and follow-up monitoring should be conducted for these patients.