The study on the use of multi-holed orifice plate for measuring flow rate is a growing area of research. As compared to standard orifice plate, multi-holed orifice plates (MO) have number of advantages, such as, these plates require minimum straight piping at the upstream without compromising the pressure losses and provide better accuracy in the measurement of flow rates. In this study, a systematic methodology is adopted for investigating the effect of different geometrical parameters on pressure loss coefficient and values of parameters under investigation varied using central composite design. The geometrical parameters chosen for the study are: (a) Number of holes; (b) Multi-hole Diameter ratio and (c) Compactness of holes. Commercial computational fluid dynamics code (ANSYS Fluent) is employed to perform simulations for 15 different settings of these parameters to analyze their effect on pressure loss coefficient and flow development length at downstream of multi-holed orifice plates. It is found that values of pressure loss coefficient is a strong function of multi-hole diameter ratio, whereas, the flow conditioning properties are strongly affected by the number of holes.