This project served as a pilot study that illustrated the feasibility of using naturalistic driving data to assess the risk of a safety-critical event (SCE) associated with prescription (Rx) and over-the-counter (OTC) drug use while driving. Results from this study showed that Rx and OTC drug use, in general, was not associated with an increased or decreased risk of involvement in an SCE. Additionally, drugs that had potential adverse effects related to driving were not found to increase the risk of involvement in an SCE. The use of caffeine was found to be associated with a decreased risk of SCE involvement in all seven half-lives (odds ratios ranging from 0.44 to 0.66). This project did show the feasibility of using a naturalistic approach to assess the risk associated with Rx and OTC use while driving.