Understanding of atomic scale interactions of molecular species with mineral surfaces is needed to bring about mineral processing innovation. In this regard, Density Functional Theory (DFT) methods are well suited. In this work, the outcome of leaching synthetic acanthite -a surrogate for a silver-containing sulfide ore- with both cyanide ion and thiourea are studied with DFT considering solvent effects. The results are correlated to the experimental percentage of silver extracted with each of the leaching agents under similar conditions of molar concentration, temperature and percentage of solids. Our calculations show both leaching reactions to be exergonic and of the same order of magnitude in Gibbs energy of reaction than values determined from thermodynamic tables. Also, less favorable Gibbs reaction energies are obtained for cyanidation in absence of oxygen and thioureation in absence of Fe(II) highlighting the impact of oxidants on the exergonicity of the respective global leaching reactions. Finally, analyzing the percentage of silver extracted from acanthite and the absolute value of Gibbs energies of the respective reaction, we conclude that the more exergonic a leaching reaction, the higher percentage of silver is extracted from acanthite, provided that there is no kinetic control of each of the leaching reactions. © Wroclaw University of Science and Technology.