Differential scanning calorimetry was used to study the effect of isotopic substitution on the eutectic and melting temperatures in the water-tetrahydrofuran (THF) system with THF molar fractions near the stoichiometry of the hydrate phase. Deuteration of the host causes an opposite effect from that of the guest with respect to the hydrate liquidus curve and eutectic melting temperature. The eutectic temperature in D2O-containing systems is approximately 3.7 K higher than that in H2O-containing systems. The melting temperatures of THF and deuterated THF hydrates increase by roughly 3.5 K with heavy water. The inclusion of deuterated THF causes a depression of the hydrate liquidus temperatures and a small but measurable effect on the eutectic temperature.