The current study aimed to assess left ventricular (LV) longitudinal systolic strains in children with KD using two-dimensional speckle-tracking imaging and to analyze the relationship of LV myocardial deformation to coronary lesions and laboratory markers. The study enrolled 101 children with acute KD. An additional 50 age- and gender-matched normal children were enrolled as control subjects. During different phases of KD, echocardiograms were recorded for 61 children. Two-dimensional strain analysis software was used to track myocardial movement and obtain the strain from each LV segment. The LV longitudinal systolic strain decreased significantly in children with acute KD but increased immediately after intravenous immunoglobulin therapy. At 6-8 weeks after the onset of KD, all LV strains had recovered to normal. The LV systolic strain was not associated with coronary dilation in either acute or convalescent KD. In acute KD, aspartate transaminase, alanine transaminase, erythrocyte sedimentation rate, C-reactive protein (CRP), and hemoglobin (Hb) were found to be associated with coronary dilation, whereas LV systolic strains were found to be correlated with elevated CRP and decreased Hb. Speckle-tracking imaging of LV systolic strain was simple and accurate in evaluating LV function during different phases of KD. No association between LV dysfunction and coronary dilation was observed, but a relationship with CRP and Hb was found. Further studies are recommended to validate the current study results and explore further how these findings can improve clinical practice.