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Background We studied the course of plasma concentrations of 4 cardiovascular biomarkers: natriuretic peptides (BNP, NT-proBNP; mid-regional (MR) pro-atrial NP); and soluble endothelial CD146 (sCD146), in patients with severe mitral valve stenosis undergoing percutaneous mitral commissurotomy (PMC) to identify potential markers of procedural success. Methods Biomarkers were tested in 40 patients the day before and the day after PMC. Success was defined as mitral valve area ≥ 1.5 cm2; or an increase of ≥0.5 cm2 in mitral valve area associated with echocardiographic mitral regurgitation Results Average age was 63.5 ± 12.7 years; 32(80%) were female. Before PMC, mean valve area was 1.1 ± 0.2 cm2, mean gradient 9.1 ± 3.5 mmHg. PMC was successful in 30 (75%) and unsuccessful in 10 (25%). PMC yielded a significant reduction in MR-proANP and sCD146, driven by a significant reduction in these biomarkers in patients with successful procedure, whereas no reduction was observed in patients with unsuccessful procedure. A significant correlation was found between changes in plasma sCD146 and the relative change in mitral valve area. Elevated pre-procedural sPAP correlated with high sCD146, and accordingly, a significant correlation between the decrease in sPAP and sCD146 after PMC was shown. Conclusions MR-proANP and plasma sCD146 decreased significantly immediately after successful PMC. They appear to be markers of immediate success of PMC and of the hemodynamic improvement achieved by this procedure in patients with MS. Trial registration This study is part of the cohorts registered with ClinicalTrials.gov on June 16, 2011 under the number NCT01374880.