The recent growth in smokeless tobacco (ST) consumption has raised questions about consumer risk perceptions of ST products, especially in high-risk vulnerable populations. This qualitative study examined risk perceptions of ST among adolescent and adult users and nonusers in Ohio Appalachia. Focus groups and interviews were held with adolescents (n = 53; M age = 17 years) and adults (n = 63; M age = 34 years) from four Ohio Appalachian counties. Participants were asked about their perceptions of ST-related health risks, ST safety, and the relative safety of ST compared with cigarettes. Transcriptions were coded independently by two individuals. Overall, participants were knowledgeable about health problems from ST use (e.g., oral cancers, periodontal disease). Nearly all participants stated that ST use is not safe; however, there was disagreement about its relative safety. Some perceived all tobacco products as equally harmful; others believed that ST is safer than cigarettes for either the user or those around the user. Disagreements about ST relative safety may reflect mixed public health messages concerning the safety of ST. Comprehensive consumer messages about the relative safety of ST compared with cigarettes are needed. Messages should address the effect of ST on the health of the user as well as those exposed to the user.