Recently, the prevalence of infant Kawasaki disease (KD) has increased. However, the myocardial functional analysis of infant KD can be difficult and rarely reported. The purpose of this study was to investigate layer specific myocardial strain analysis for better assessment of the acute period in infant KD. The study retrospectively reviewed the echocardiographic data of 25 infant patients with KD at the acute phase. With advanced imaging, pulsed tissue Doppler velocity data, myocardial strain with three layers specific analysis was performed. Then the data were compared with 25 age-matched healthy control infants. The measures of longitudinal strain and radial strain were decreased in infant KD compared to healthy controls. The circumferential strain was significantly decreased in infant KD at all three myocardial layers, especially in the endocardial layer (KD: −20.5 ± 6.4 % vs. control: −25.6 ± 7.6 %, endocardium, p = 0.00001; −14.6 ± 4.4 % vs. −18.1 ± 4.0 %; middle myocardium, p = 0.01; −9.7 ± 3.3 % vs. −11.4 ± 3.8 %; epicardium, p = 0.04). The acute phase of infant KD demonstrated decreased myocardial strain measurement. Circumferential strain was the lowest in the endocardial layer. Further continuous long-term follow up for myocardial assessment should be recommended even after recovery with appropriate treatment.