Incorrect use of acetaminophen that results in severe liver injury is among the most common adverse drug events (ADEs) in the United States of America (USA), and other countries around the world. Compared to any other drug, it is also on the top for emergency calls, emergency room visits, and acute liver failure in the USA. Consequently, regulating acetaminophen has become a heated and unresolved public debate. During the last decades, multiple efforts have taken place to address the issue, mostly focused on the premise that inappropriate labeling is a leading cause of such ADEs, for failure in communicating the associated risks through warnings. Unlike previous studies, this paper illustrates the importance of considering human factors principles. Three different warning labels were designed and evaluated. The results showed no statistically significant effect, despite the application of best practices for label warning design. Non-design factors, the warning process and why a warning could fail are also illustrated. Implications could help researchers, policy makers, and manufacturers to consider focusing less on traditional labeling interventions, and to invest efforts more systematically considering also the current trends and the current needs of consumers.