Purpose of the project was to test a Web-based program designed to prevent prescription drug misuse. Study sample consisted of 346 working women randomized into either an experimental or wait-list control condition. Analysis of covariance and logistic regression were used to compare responses. Women receiving the intervention had greater knowledge of drug facts and greater self-efficacy in medication adherence and ability to manage problems with medications compared with controls. Women receiving the intervention also had reduced symptoms reported on the CAGE for prescription medications. Findings suggest that multimedia Web-based programs can be a beneficial addition to substance misuse prevention services. The study's limitations are noted.