In thermal analysis, the apparatus commonly used to quantitatively measure enthalpy change is the DSC while the DTA equipment is used for qualitative measurements. In this work a new method, called the “mass-difference baseline method”, is proposed to attempt to use DTA for quantitative measurement. The presented method employs the DTA curve derived from a small mass sample as the baseline for a large mass sample using the same material. Such an approach diminishes the asymmetric heat transfer problem attributed to the “apparatus effect” and “sample influence”, thus greatly improving the linearity between the DTA curve and enthalpy change. The theoretical basis of this method is presented and discussed in this paper. The method has been tested for the determination of the enthalpy change of graphite and elastomers over a large temperature range from 30°C to 600°C. Compared with DSC, one important advantage of this method is that it allows enthalpy measurement to be carried out in an open system allowing a sample mass loss during the measurement. For example, during the measurement of elastomers, intensive decomposition and 70% of the sample mass loss occur. The DTA quantitative measurement successfully determines the heat capacity changes as well as the heat of reaction and heat of evaporation, which all occur during the enthalpy changes of the material subjected to decomposition. However, the accuracy of this method is still not high enough for high accurate enthalpy measurement.