Gender has been proposed to impact the phenotype and prognosis of hypertrophic cardiomyopathy (HC). Our aims were to study gender differences in the clinical presentation, phenotype, genotype, and outcome of HC. This retrospective single-center cohort study included 1,007 patients with HC (62% male, 80% genotyped) evaluated between 1977 and 2017. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard regression models. At first evaluation, female patients presented more often with symptoms (43% vs 35%, p = 0.01), were older than male patients (56 ± 16 vs 49 ± 15 years, p <0.001), and more frequently had hypertension (38% vs 27%, p <0.001), left ventricular outflow tract obstruction (37% vs 27%, p <0.001), and impaired left ventricular systolic (17% vs 11%, p = 0.01) and diastolic (77% vs 62%, p <0.001) function. Overall, the genetic yield was similar between genders (54% vs 51%, p = 0.4); however, in patients ≥70 years, the genetic yield was less in women (15% vs 36%, p = 0.03). During 6.8-year follow-up (interquartile range 3.2 to 10.9), female gender was not independently associated with all-cause mortality (HR 1.25 [0.91 to 1.73]), cardiovascular mortality (HR 1.22 [0.83 to 1.79]), heart failure-related mortality (HR 1.77 [0.95 to 3.27]), or sudden cardiac death (SCD) and/or aborted SCD (HR 0.75 [0.44 to 1.30]). Interventions and nonfatal clinical events did not differ between the genders. In conclusion, female patients with HC present at a more advanced age with a different clinical, phenotypic, and genetic status. There is no independent association between female gender and all-cause mortality, cardiovascular mortality, heart failure-related mortality, or SCD.