This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = 65) infants were enrolled in this study. Tibial bone SOS was measured using quantitative ultrasonography (QUS) on the left tibia of newborn infants after birth (within 7 days), at 1 month old, and then every 2 months until subjects were approximately 12-15 months old. Follow-up checks included anthropometric measurements and tibial bone SOS. Mean tibial bone SOS at birth was significantly higher in term infants (mean ± SD, 2968.5 ± 99.7 m/s) than in preterm infants (2912.2 ± 122.6 m/s). Values of follow-up tibial bone SOS declined for the first 4 months, and then increased gradually until 12-15 months old. This increasing trend was greater in preterm infants after 2 months of corrected age than in term infants. There were no significant differences by 12-15 months of age between preterm and term infants. A longitudinal mixed-effect model controlling for internal correlations and other covariates in the two groups showed that age and the SOS value at birth were important factors affecting the tibial bone SOS in both preterm and term newborn infants during infancy. There are significant differences in the pattern of change in tibial bone SOS values between preterm and term infants during the first 12-15 months of life. Age and SOS value at birth were important factors affecting the pattern of tibial bone SOS change in both preterm and term newborn infants during infancy.