Background: Severe mitral regurgitation (MR) is associated with reduced afterload and overestimated ejection fraction (EF). Correction of MR may result in significant decline of EF in some patients. Aim: Determine the predictors of postoperative decline of EF in patients with severe MR after mitral valve surgery. Methods: From April 2011 to April 2012, we prospectively recruited 30 consecutive patients with isolated primary severe MR who had successful mitral valve surgery (repair in 19 patients including 10 patients with rheumatic etiology and replacement with mechanical prosthesis with chordal preservation in the remaining patients). Clinical data were collected including the presence of atrial fibrillation (AF) and functional capacity using 6-minute walk test (6MWT). Echocardiography was done to study the left ventricular (LV) volume, EF, and left atrial volume. We performed pulsed wave tissue Doppler imaging (TDI) to measure lateral mitral annulus peak S wave velocity and myocardial performance index (MPI). Follow up echocardiogram was done two months after surgery to asses postoperative EF. Patients with post-operative EF<50% (Group I) were compared with patients with post-operative EF ≥50% (Group II) using independent sample T test for continuous variables and Chi square test for categorical variables. Results: The mean age of patients was 33±12.7 years and 63.3% were females. The cause of MR was rheumatic in 20 patients, myxomatous in 10 patients. The effective regurgitant orifice area was 0.46±0.17 cm2. The pre-operative biplane EF was 63±6.7%. Compared to Group II, patients in Group I (n=9) had significantly more AF (p=0.008), shorter 6MWT distance (p=0.009), larger LV end-systolic volume (p=0.047), larger LA volume index (p=0.008) and lower pre-operative EF (p=0.004). However, the TDI peak S wave velocity and MPI were not different between the two groups (p=0.06 and p=0.27 respectively). Multiple linear regression analysis using stepwise technique showed that the preoperative biplane EF and the 6-minute walk distance are independent predictors of postoperative EF<50% with p value 0.007 and 0.013, respectively. The receiver operating characteristic (ROC) curve analysis showed that a pre-operative biplane EF< 61% has 76.2 sensitivity and 78% specificity and a 6-minutes’ walk distance < 245 meters has 87.5% sensitivity and 75% specificity to predict a post-operative LV EF< 50%. Conclusion: Pre-operative LV biplane EF <61% and 6-minute walk distance < 245 meters are independent predictors of postoperative LV systolic dysfunction (EF<50%) after mitral valve surgery for severe mitral regurgitation.