We investigate the optimization of removal of silver from anode slime in ammonium thiosulfate solutions by microwave using statistical design methods. Ammonium thiosulfate concentration, leaching temperature, solid-to-liquid ratio and leaching time were selected as variables. A model was obtained among relevant parameters by means of variance analysis by using the Matlab Computer Software Programme. The optimum conversion conditions for process were found to be ammonium thiosulfate (ATS) concentration of 0.4 M, leaching temperature of 313 K, solid-to-liquid ratio of 1/10, leaching time of 90 min, and stirring speed of 500 rpm. Under optimal conditions, the removal of silver is obtained as 88.769%. It is observed that the model obtained has nearly fitted the full second-order model, and the correlation coefficient calculated at the 95% confidence level has a value of 0.97.