This paper reports utilization of differential scanning calorimetry measurements to evaluate binding constants for Human Serum Albumin of 28 different drug ligands. Protein/ligand mixtures were prepared at various ligand concentrations and subjected to thermal denaturation analysis by calorimetry. From the measurements, the melting temperature, Tm, and free-energy ΔGcal(37°C) for melting ligand-bound Albumin were evaluated as a function of ligand concentration. Concentration dependent behaviors of ΔGcal(37°C) and Tm derived from protein/ligand mixtures were used to construct dose-response curves. Model fits of dose-response curves yielded quantitative evaluation of the ligand binding constant, KD, and semi-quantitative estimates of the binding stoichiometry, n. Many of the ligands had known binding affinity for Albumin with binding constants reported in the literature. Evaluated Albumin binding parameters for the ligands impressively agreed with reported literature values determined using other standard experimental methods. These results demonstrated utility of our calorimetry-based process for applications in pre-clinical drug screening.