Prosthesis-patient mismatch (PPM) is associated with dismal prognosis after aortic valve replacement (AVR). Sex differences in PPM outcomes remain poorly explored. Therefore, this study aims to evaluate sex-specific impact in PPM after surgical AVR. Between 2000 and 2021, 7319 patients underwent surgical AVR at the Institut Universitaire de Cardiologie et de Pneumologie de Québec. Prosthesis-patient mismatch was defined by using the indexed effective orifice area (EOAi) and by applying the Valve Academic Research Consortium-3 (VARC-3) criteria. The cohort was followed up prospectively from surgical AVR until November 2023. The primary endpoint was defined as long-term mortality and the secondary endpoint as long-term cardiovascular (CV) and perioperative mortality. Mortality was established and CV mortality was adjudicated by Quebec national database. Any-degree PPM resulted more prevalent in women than in men (31.9% vs. 19.7%, P < .0001) with rare incidence of severe PPM (2.4% vs. 0.6%, P < .0001) according to VARC-3 definition. Over a median follow-up of 12.6 years, there were 3231 (44.1%) all-cause deaths, with 1238 (16.9%) from CV causes. Prosthesis-patient mismatch was associated with all-cause mortality (hazard ratio 1.30, 95% CI 1.20-1.40; P < .0001) and CV mortality (hazard ratio 1.39, 95% CI 1.23-1.57; P < .0001) in the whole cohort without interaction between sexes (P ≥ .74). After comprehensive multivariable adjustment, VARC-3 PPM remained independently associated with outcome only in women (P ≤ .04). Adapting PPM definition according to spline-derived EOAi thresholds disaggregated by sex, PPM was independently associated with outcome in both sexes (P ≤ .04). Sex-specific EOAi thresholds associated with outcomes emerged in this large regional study. This finding suggests that PPM definition in men may follow higher EOAi thresholds than in women.