Background We implemented sophisticated color M-mode analysis to assess age-dependent progression of left ventricular (LV) diastolic function. Methods Normal infants were prospectively enrolled for serial echocardiograms at 1 week, 1 month, 6 months, 1 year, and 2 years. From color M-mode scans, propagation velocity (V-P), strength of filling (V-S), and intraventricular pressure difference (IVPD) in 3 segments along apex-to-mitral valve scan line were measured. Results Age-wise comparisons of diastolic filling from 121 echocardiograms in 31 infants showedV(P)(cm/s),V-S(cm(2)/s), and E-wave IVPD (mmHg) at 1 week to be 66.2 +/- 11.9, 75.3 +/- 19.9, and 1.5 +/- 0.4, respectively, whileV(P),V-S, and E-wave IVPD at 1 month were 80.3 +/- 14.4, 101.2 +/- 28.3, and 2.42 +/- 1.1, respectively. There were significant differences inV(P)and segmental IVPD between first week and first month (p < 0.005) and IVPD between the age groups (p < 0.001). Conclusions Comprehensive analysis of transmitral color M-mode data is feasible in infants, enabling calculation of pressure drop between the LV base and apex and strength of propagation from two distinct slopes. Profound changes very early followed by relatively constant filling mechanics in later infancy indicate significant LV maturation occurring during the first month of life. Impact We implemented sophisticated analytic methods for color M-mode echocardiography in infants to assess age- and dimension-dependent changes in left ventricular diastolic function. Comprehensive characterization of transmitral color M-mode flow was feasible, enabling calculation of pressure drop between left ventricular base and apex and strength of propagation. Left ventricular diastolic filling function has predictable maturational progression, with significant differences in the intraventricular pressure between infants from birth to 2 years. This study forms the basis for future studies to examine alteration of early diastolic filling in congenital heart disease.