ABSTRACT: The management of mitral regurgitation (MR) is challenging - patients may be asymptomatic, oligosymptomatic, older with comorbidities, or clinically symptomatic and not appropriate for surgery. The current review assesses morbidity, mortality, and risk factors associated with functional and organic MR, with a focus on severe MR.A structured literature review was conducted in MEDLINE, Embase, the Cochrane Library, and via hand-searching of conference proceedings. Prospective randomised controlled trials and observational studies including adult patients with MR reporting on treatment response rates, survival, time-to-treatment failure, quality of life, and adverse events were eligible for inclusion.In total, 32 publications met the inclusion criteria (9 in functional, 18 in organic, and 5 in functional/organic). Despite study heterogeneity, an increased risk of mortality and morbidity was observed which increased with MR severity. Risk factors associated with mortality and morbidity included advancing age, presence of atrial fibrillation, increasing effective regurgitant orifice, ejection fraction, left ventricle end systolic diameter, diabetes, and increasing New York Heart Association class.The current review represents one of the most comprehensive conducted in the medical/conservative management of MR. An increased risk of mortality and morbidity, which appeared to rise with greater severity, was associated with MR (versus no MR). An unmet need exists in the management of patients with severe symptomatic MR and a high surgical risk as they have a poor prognosis and limited treatment options. Further research into alternative medical strategies and patient management is needed to improve prognoses and reduce mortality and morbidity.