In many cases, the application of multiple safety-related improvements results in greater crash reduction benefits. This results in the possibility of multiple CMFs being applicable. The interaction between various safety treatments is complicated and can make it difficult to determine the true effectiveness of multiple treatments when used together. This is because CMFs are not always independent of one another, and it is possible to overestimate or underestimate the potential for crash reduction when applying the effects of multiple CMFs. A CMF is considered independent of another CMF if there is no overlap in their crash type and/or crash severity. For example, the installation of a pedestrian signal would be relatively independent of the installation of a left-turn phase at an adjacent intersection, because one addresses pedestrian-vehicle crashes while the other addresses left-turn opposite-direction crashes. An example of overlapping or non-independent CMFs would be multiple treatments focused on reducing nighttime crashes or multiple treatments focused on reducing run-off road crashes.

When applying multiple treatments, no more than three CMFs can be applied because it may overestimate the reduction of crashes. The following subsection provides an overview of four different methods that can be considered when applying multiple CMFs.