Summary: In this paper we present direct numerical simulations (DNS) of hypersonic turbulent boundary layers to study high-enthalpy effects. We study high- and low-enthalpy conditions, which are representative of those in hypersonic flight and ground-based facilities, respectively. We find that high-enthalpy boundary layers closely resemble those at low enthalpy. Many of the scaling relations for low-enthalpy flows, such as van-Driest transformation for the mean velocity, Morkovin’s scaling and the modified strong Reynolds analogy hold or can be generalized for high-enthalpy flows by removing the calorically perfect-gas assumption. We propose a generalized form of the modified Crocco relation, which relates the mean temperature and mean velocity across a wide range of conditions, including non-adiabatic cold walls and real gas effects. The DNS data predict Reynolds analogy factors in the range of those found in experimental data at low-enthalpy conditions. The gradient transport model approximately holds with turbulent Prandtl number and turbulent Schmidt number of order unity. Direct compressibility effects remain small and insignificant for all enthalpy cases. High-enthalpy effects have no sizable influence on turbulent kinetic energy (TKE) budgets or on the turbulence structure.