When designing a medical device based on lightweight accelerometers, the designer is faced with a number of questions in order to maximize performance while minimizing cost and complexity: Where should the inertial unit be located? How many units are required? How is performance affected if the unit is not correctly located during donning? One way to answer these questions is to use position data from a single trial, captured with a nonportable measurement system (e.g., stereophotogrammetry) to simulate measurements from multiple accelerometers at different locations on the body. In this paper, we undertake a thorough investigation into the applicability of these simulated acceleration signals via a series of interdependent experiments of increasing generality. We measured the dynamics of a reference coordinate frame using stereophotogrammetry over a number of trials. These dynamics were then used to simulate several “virtual” accelerometers at different points on the body segment. We then compared the simulated signals with those directly measured to evaluate the error under a number of conditions. Finally, we demonstrated an example of how simulated signals can be employed in a system design application. In the best case, we may expect an error of between a derived virtual signal and that directly measured by an accelerometer. In practice, however, using centripetal and tangential acceleration terms (that are poorly estimated) results in an error that is an order of magnitude greater than the baseline. Furthermore, nonrigidity of the limb can increase error dramatically, although the effects can be reduced considerably via careful modeling. We conclude that using simulated signals has definite benefits when an appropriate model of the body segment is applied.