Percutaneous coronary interventions (PCIs) are increasingly being used to treat unprotected left main coronary artery (ULMCA) lesions. However, research is sparse on the acute changes of left ventricular (LV) hemodynamics and function during PCI in patients with ULMCA stenosis. We aimed to assess the acute changes of LV function using speckle-tracking imaging during PCI in these patients. Fifteen consecutive patients who underwent elective PCI for ULMCA stenosis were enrolled. Echocardiographic studies and pressure measurement were performed at baseline, during PCI and after PCI. LMCA occlusion with a first balloon inflation induced a marked reduction in the peak positive derivative of LV pressure (dP/dt max), LV global longitudinal strain (GLS), and systolic and diastolic strain rates, and a marked increase in LV end-diastolic pressure (EDP) (all P < 0.01). During the second inflation, the degrees of LV hemodynamic and functional changes were similar to those of the first inflation, even with a higher inflation pressure. During the third inflation, the values of GLS and dP/dt max were higher than those of the second inflation (P = 0.03 and P = 0.05, respectively). After optimal PCI, dP/dt max, LVEDP, and strain parameters were improved to baseline values. LV hemodynamics and function were considerably impaired with the first ballooning during PCI for ULMCA stenosis. However, the degrees of LV hemodynamic and functional changes decreased with each successive balloon inflation, which can be explained by ischemic preconditioning. After all procedures were safely completed, LV systolic function was improved without LV diastolic stunning.