Abstract: Methods and related program product for assessing and optimizing metrology instruments by determining a total measurement uncertainty (TMU) based on precision and accuracy. The TMU is calculated based on a linear regression analysis and removing a reference measuring system uncertainty (URMS) from a net residual error. The TMU provides an objective and more accurate representation of whether a measurement system under test has an ability to sense true product variation. The invention also includes a method for determining an uncertainty of the TMU.