Left ventricular (LV) myocardial work (LVMW) indexes have shown incremental value over LV ejection fraction and were found to have prognostic significance in patients with secondary mitral regurgitation. We therefore aimed to investigate the association between LVMW indexes and forward flow reserve in patients with secondary mitral regurgitation, treated with transcatheter edge-to-edge repair (TEER). LVMW indexes were evaluated at baseline and forward stroke volume index (FSVI) was evaluated at baseline and 6-month follow-up after TEER. Patients were divided in 2 groups: improvers (improvement in FSVI ≥20%) and nonimprovers (improvement in FSVI <20%). A total of 70 patients (median age 76 years, 59% men) were included. FSVI was the only echocardiographic parameter that improved after TEER. There was a significant decrease in LV global longitudinal strain in the nonimprovers (p = 0.002) but not in the improvers (p = 0.177). Global work index and global constructive work worsened in nonimprovers (p = 0.005 and p = 0.004, respectively), whereas no difference was seen in these indexes in improvers (p = 0.093 and p = 0.112, respectively). Global work efficiency remained independently associated with forward flow reserve after adjusting for a variety of potential confounders. In conclusion, FSVI nonimprovers demonstrated worsening of LV systolic function after TEER compared with improvers, in whom LV systolic function remained stable. Global work efficiency was associated with FSVI improvement after TEER, independent of LV systolic function.