Percutaneous mitral valve repair (PMVR) is an interventional treatment option in patients with severe mitral regurgitation (MR) and at high risk for open-heart surgery. Currently, limited information exists about predictors of procedural success after PMVR. Galectin-3 (Gal-3) and suppression of tumorigenicity 2 (ST2) induce fibrotic alterations in severe MR and heart failure. We sought to examine the predictive value of Gal-3 and ST2 as specific indicators of therapeutic success in high-risk patients undergoing PMVR. We hypothesize that extended cardiac fibrotic alterations might have impact on successful MR reduction after the MitraClip procedure. A total of 210 consecutive patients undergoing PMVR using the MitraClip system were included in this study. Procedural success was defined as an immediate reduction of MR by ≥2 grades, assessed by echocardiography. Venous blood samples were collected prior to PMVR and at 6 months follow-up for biomarker analysis. After PMVR there was a significant reduction in the severity of MR (MR grade: 3 ±0.3 vs 1.6 ±0.6, P <0.001). Low baseline Gal-3 levels (PMVRsuccess : 22.0 ng/mL [IQR, 17.3-30.9] vs PMVRfailure : 30.6 ng/mL [IQR, 24.8-42.3], P <0.001) and ST2 levels (PMVRsuccess : 900.0 pg/mL [IQR, 619.5-1114.5] vs PMVRfailure : 1728.0 pg/mL [IQR, 1051.March 1, 1930], P < 0.001) were associated with successful MR reduction after PMVR. Also, ROC analysis identified low baseline Gal-3 and ST2 levels as predictors of therapeutic success after PMVR (AUCGal-3 :0.721 [IQR, 0.64-0.803], P < 0.001; AUCST2 : 0.807 [IQR, 0.741-0.872], P < 0.001). There was an association between low Gal-3 and ST2 plasma levels and successful MR reduction in patients with severe MR undergoing PMVR using the MitraClip system.