The protective effect of severe mitral regurgitation (MR) against left atrial thrombus formation has been well documented. It was also proposed that severe MR may prevent thrombus formation within the left ventricle (LV) with systolic dysfunction. Therefore, we investigated whether ischemic MR prevents thrombus formation within the LV in patients with systolic dysfunction. The study population was comprised of 1313 patients (1133 males, 180 females, age 56+/-18) with ischaemic LV dysfunction documented by coronary angiography and left ventriculography. None of the patients had a history of chronic anticoagulation. Epicardial coronary arteries were normal in 91 patients, and single-vessel, two-vessel, and triple-vessel disease were detected in 328, 330, and 564 patients, respectively. Left ventricular thrombus and severe MR were detected in 191 (14.5%) and 125 (9.5%) patients, respectively. Overall incidence of LV thrombus was lower in patients with severe MR than in patients without severe MR (4% vs 15.6%, OR: 0.2, P<0.001). Severe MR compared with absence of severe MR was associated with a lower incidence of LV thrombus both in patients with ischemic dilated cardiomyopathy (6.8% vs 34.2%, OR: 0.19, P<0.001), and in patients with aneurysm (3% vs 18%, OR: 0.14, P<0.0001) involving anterolateral, septal and/or apical LV segments. A similar trend without statistical significance was also observed in patients with dyskinesia (4.7% vs 16%, OR: 0.26, P=0.1) related to anterolateral, septal and/or apical LV segments. However, MR had no impact on the incidence of LV thrombus in patients with aneurysm or dyskinesia related to posterior and/or inferior segments (3.7% vs 3%, OR: 1.2, P>0.05). In conclusion, severe MR seems to prevent LV mural thrombus formation in patients with ischemic dilated cardiomyopathy, and in patients with aneurysm related to anterolateral, septal, and/or apical LV segments. This relative risk reduction may be associated with diastolic volume overloading due to severe MR which may overcome stagnation and a procoagulant state within the LV with severe systolic dysfunction.