The researchers tried to use the result of multiple markers assays in maternal serum to establish a mathematical method for calculating the risk of carrying a fetus with Down syndrome. This screening method is dependent on distribution of few parameters. We investigated the effect of different set of parameters on screening system. The most popular protocol for triple marker screening of Down syndrome is based on multivariate gaussian distribution. This study has been applied in a private medical laboratory. The result of different set of distribution of parameters on efficacy and reliability of system is investigated by graphical display and simulation by monte carlo method. In some cases, different sets of parameters in protocols make calculated risk inappropriately different. In some ranges of biochemical markers, the behavior of system violates their general trends on risk calculation. We found inherent error in models. This could be explained by interaction and value of distribution of parameters. We show effect of distribution of parameters in mathematical model, estimate efficacy of system and also emphasize on quality of parameters.