Background/Aims: Mitral regurgitation (MR) is frequently observed in patients with acute myocardial infarction (AMI), and is known to convey an adverse prognosis. We sought to clarify the relationship between MR and left ventricular (LV) remodeling, in association with serum C-reactive protein (CRP) elevation. Methods/Results: A total of 181 patients with first anterior ST-elevation AMI were examined. MR was detected in 68 patients by color Doppler echocardiography 2 weeks after AMI, and the patients with MR were associated with higher incidence of readmission for heart failure. Serum CRP was serially measured, and the peak serum CRP level was markedly increased in patients with MR compared with those without MR. Multiple logistic regression analysis showed that peak CRP tertile was an independent determinant of MR after AMI (p < 0.0001). In the substudy, the increases in LV end-diastolic volume and sphericity index were higher in patients with MR than in those without MR. Conclusions: MR during the early phase of anterior AMI was associated with LV spherical change and late-phase heart failure, in association with increased serum CRP level. These findings suggest an important role of the inflammatory response in the development of ischemic MR and LV remodeling.