Objectives: Mitral regurgitation (MR) is the second most common valve disease in Europe, and differences between men and women have been described in relation to aetiology or management, which might impact the decision for intervention and patients’ clinical and economic outcomes. Thus, the objective was to analyse the burden of MR in Spain by aetiology and sex, and the management of all patients suffering from MR being admitted to hospital between 2016–2021. Methods: An analysis was carried out with the Ministry of Health’s database, including all patients in public and subsidised hospitals and defining two groups, general MR and those patients undergoing Transcatheter Edge-to-Edge repair (TEER), using a descriptive analysis of patients’ characteristics, use of resources, and outcomes; standardised rates were calculated and observed outcomes were described. Results: Hospital admissions increased from 2016 (n = 32,806) to 2021 (total n = 61,036). In general, the women were older and presented more complications. The majority of patients suffered from degenerative MR (DMR) (n = 183,005, 59.55%), and 61.56% were women, contrary to functional MR (FMR) (n = 124,278), which consisted of 62.15% males. In total, 1,689 TEERs were performed, 23.33% of them in urgent admissions, and mostly in men (65.66%). All groups showed higher rates of intervention for males. Regarding costs, women presented lower mean costs in the general MR groups but those undergoing TEER presented, in all cases, costs higher than men. Conclusions: MR entails a significant burden for patients and the Spanish healthcare system, increasing over the period of study. Differences in aetiologies by sex have been found in patients’ characteristics as well as outcomes. Further studies are needed to optimise patients’ management and their outcomes in relation to sex and aetiology.