Objectives: We sought to evaluate the effect of gender on biology, therapeutic decisions, and survival in patients with severe aortic regurgitation (AR). Background: Gender affects adaptive response to the presence of valvular heart diseases and therapeutic decisions. The impact of these on survival in severe AR patients is not known. Methods: This observational study was compiled from our echocardiographic database which was screened (1993–2007) for patients with severe AR. Detailed chart reviews were performed. Mortality data were obtained from the Social Security Death Index and analyzed as a function of gender. Results: Of the 756 patients with severe AR, 308 (41%) were women. Over a follow-up of up to 22 years, there were 434 deaths. Women compared to men were older (64 ± 18 vs. 59 ± 17 years,p= 0.0002). Women also had smaller left ventricular (LV) end diastolic dimension (5.2 ± 1.1 vs. 6.0 ± 1.0 cm,p< 0.0001), higher EF (56% ± 17% vs. 52% ± 18%,p= 0.003), higher prevalence of diabetes mellitus (18% vs. 11%,p= 0.006), and higher prevalence of ≥2+ mitral regurgitation (52% vs. 40%,p= 0.0008) despite a smaller LV size. Women were also less likely to receive aortic valve replacement (AVR) (24% vs. 48%,p< 0.0001) compared to men and had a lower survival on univariate analysis (p= 0.001). However, after adjusting for group differences including AVR rates, gender was not an independent predictor of survival. However, the survival benefit associated with AVR was similar in both women and men. Conclusions: This study strongly suggests that female gender is associated with different biological responses to AR compared to men. There is also a lower AVR rate in women, but women derive similar survival benefit as men with AVR. Gender does not seem to affect survival in an independent fashion in patients with severe AR after adjusting for group differences and AVR rates.