This work is concerned with the correlation and prediction of excess molar enthalpies, HEm, using DISQUAC. The physical basis of the model, the fitting procedure and a detailed summary of HEm results for 250 binary systems and 32 ternary mixtures is given. A systematic comparison with UNIFAC (Dortmund version) is also included. For the binary mixtures studied, the mean relative standard deviation obtained using DISQUAC is 0.086, and 0.070 for the ternary systems. UNIFAC values are 0.306 and 0.162, respectively. DISQUAC can be successfully applied to many different mixtures with HEm values ranging between (−8400 to 2800) J mol−1. Larger deviations between experimental and theoretical results are encountered for mixtures characterized by low |HEm| values arising from the differences between positive and negative contributions to HEm. The temperature dependence of HEm is well represented, although for alkan-1-ol+alkane mixtures, DISQUAC overestimates CEpm (isobaric excess molar heat capacities) values outside the temperature interval of (268.15 to 318.15) K. In particular, DISQUAC results are better than UNIFAC calculations for systems involving cyclic or aromatic molecules; or alkylated aromatic compounds; or compounds characterized by strong intramolecular effects, or solutions including primary, secondary or tertiary alcohols.