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Aims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes. Methods Patients with significant secondary MR, of both ischaemic and non-ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all-cause mortality. Results A total of 698 patients (mean age 66 ± 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non-ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 ± 4.1% vs. 7.5 ± 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow-up of 57 [interquartile range 29–110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1-, 2- and 5-year follow-up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001). Conclusions Significant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis. [ABSTRACT FROM AUTHOR]