In this research, Design of Experiment (DOE) was employed to investigate the influence of operational parameters (e.g. leaching time, particle size and cyanide concentration) on gold cyanidation process of three pit samples. The gold content of the pit samples were 13.13 g/t, 3.28 g/t and 7.83 g/t respectively for Prestea underground ore (Pit A), Beta North Oxide ore (Pit B) and Mampong Transition ore (Pit C). Design of Experiment (DOE) was employed to design leaching (bottle roll) test, model and evaluate the influence of particle size, cyanide concentration and leaching time on the cyanidation of the three pit samples. The particle size, cyanide concentration and leaching time were varied from d80 of 150 to 75 µm, 120 to 500 ppm and 3 to 24 hrs respectively. Leaching of the samples (in the absence of activated carbon) for 24 hrs gave recoveries below 88%. Thus, recoveries for Pit A, Pit B and Pit C were 87%, 75% and 51% respectively. Simulation of the results using DOE at 95% confidence level to predict the relationship between the gold recoveries and influential parameters showed that gold recovery correlates positively with cyanide concentration and residence time. In terms of particle size, gold recovery was observed to increases marginally with decreasing particle size from 106 to 75 µm. A confirmatory test performed showed that not much difference in Au recovery is observed upon fine grinding (i.e. from 80% passing 106 µm to 80% passing 75 µm) and Carbon in leach (CIL) of the three Pit samples significantly improved Au recoveries. The findings from the study suggest that DOE could be used for cyanide amenability studies.