Understanding the tribological interactions between shoe and floor materials is important in order to enhance shoe and floor design and to prevent slip and fall accidents during walking. In the present investigation, experiments were conducted using a custom developed pin-on-disk type tribometer to understand the influence of boundary and hydrodynamic properties on the shoe-floor materials’ coefficient of friction. Specifically, polyurethane shoe material was slid against vinyl floor material in the presence of varying lubricants (i.e., water, detergent, three diluted glycerol concentrations, and canola oil). The experiments were conducted for a range of biologically relevant sliding velocities from 0.05 m sec−1 to 1.0 m sec−1 at a contact pressure of 266.1 kPa under ambient conditions. The fluid chemical composition appeared to affect the boundary friction coefficient with longer-chain molecules resulting in a decreased coefficient of friction. As fluid viscosity increased, the rate of coefficient of friction decay increased with respect to increasing fluid entrainment velocity, suggesting less material contact and increased film thickness. The nondimensional film thickness under all conditions was calculated and the nondimensional film thickness consistently increased with increased viscosity and speed. Additionally, the effect of functionally achievable variations in polyurethane shoe roughness on the coefficient of friction was examined and found to have no statistically significant effect on boundary or hydrodynamic contributions to the coefficient of friction.