BACKGROUND: Little is known about the effect of sex on functional status decline in aortic valve stenosis (AS) patients. OBJECTIVES: The purpose of this study was to examine the changes in functional status according to sex in patients with mild-to-moderate AS and its association with the composite of death or aortic valve replacement (AVR). METHODS: We included patients with mild-to-moderate AS prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study (NCT01679431). Functional status was assessed using the New York Heart Association classification and the Duke Activity Status Index (DASI). RESULTS: A total of 244 patients (mean age 64 ± 14 years, 29% women) were included. The mean follow-up was 4.3 ± 2.4 years. Women with intermediate-to-fast AS progression rate (median change in peak aortic jet velocity ≥0.11 m/s/year) had significantly faster decline in DASI score compared to men with similar progression rate ( < 0.05). In linear mixed analysis adjusted for several clinical and echocardiographic factors, female sex and change in peak aortic jet velocity remained strongly associated with the worsening of New York Heart Association class and the decline of DASI score (all,  < 0.001). The composite of death or AVR occurred in 115 patients (16 deaths and 99 AVRs). In multivariable Cox regression analyses, functional status decline during follow-up remained significantly associated with the composite of death or AVR (HR: 2.13; 95% CI: 1.22-3.73;  = 0.008). CONCLUSIONS: In patients with mild-to-moderate AS at baseline, intermediate-to-fast progression rate of AS was associated with a more rapid decline of functional status during follow-up, particularly in women. Functional status decline during follow-up was strongly associated with the incidence of death or AVR, with comparable effect in both women and men.