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BACKGROUND: Patients with a mechanical heart valve (MHV) require vitamin K antagonist (VKA) treatment to prevent thromboembolism. OBJECTIVES: To examine the quality of VKA treatment and clinical outcomes, including all-cause mortality, bleeding, and thromboembolism, by sex and age in patients with an MHV. METHODS: Data from 17 Dutch anticoagulation clinics were linked to Statistics Netherlands. Patients with an MHV receiving VKAs between 2013 and 2019 were included and followed from the first MHV hospitalization discharge until death, VKA discontinuation, or December 31, 2019. Quality of treatment was assessed by the time in therapeutic range (TTR) and international normalized ratio variability (variance growth rate). Clinical outcomes were identified by first in-hospital diagnoses and primary causes of death and expressed as incidence rates (IR) per 100 person-years, stratified by sex and age. RESULTS: In total, 3527 MHV patients (38% women, median age 67 years) had a median follow-up of 3.0 years. Women <55 years (n = 228) had lower TTR compared with the other sex and age groups. All-cause mortality rates were similar across the sexes in both age groups. Women aged <55 years had a higher IR (95% CI) of both bleeding (2.52 [1.49-3.98] vs 1.03 [0.51-1.84]) and thromboembolism (2.83 [1.73-4.38] vs 1.70 [1.01-2.69]) than similarly aged men (n = 395). However, treatment quality and IR were similar for women and men aged ≥55 years. CONCLUSION: Women with MHVs aged <55 years exhibited poorer quality of VKA treatment and higher rates of complications than similarly aged men. These findings highlight the need for tailored anticoagulation strategies in younger female MHV patients.