The state of Mississippi is undergoing a prescription opioid epidemic that mimics national trends in which prescribing rates are dropping, yet overdoses involving opioids remain high. In response to the state’s crisis, the PReventing Opioid Misuse In the SouthEast (PROMISE) Initiative was created to provide education for preventing the misuse of prescription opioids. A mail survey and post card intervention were distributed in six Appalachian counties in the state to gather the self-reported attitudes, norms, and perceived behavioral control of residents as it related to using a prescription drug take-box. Descriptive and multivariable analyses indicate the intervention did not increase intention to use prescription drug take-back boxes as a method of disposal. Lack of awareness and inconvenience remain common themes among individuals who chose not to use take-back boxes. Thus, researchers recommend future interventions incentivize prescription disposal.