This paper investigates the ability of a shear wave reflection (WR) method to monitor microstructural changes of Portland cement mortar during hydration. The wave reflection method measures the reflection loss of shear waves at an interface between a steel plate and mortar. Mortars with water/cement ratios of 0.35, 0.5 and 0.6 were tested at isothermal curing conditions of 25 °C. The numerical model HYMOSTRUC3D was used to simulate the evolution of microstructural properties of the cement paste phase of the tested mortars. The parameters obtained from the simulations were the volume fraction of the total and connected solid phase and the specific contact area of the hydrated cement particles. The investigations have shown that the wave reflection measurements are governed primarily by the degree of the inter-particle bonding of the cement particles as calculated from the specific contact area of a simulated microstructure.