© 2020 The Author(s). Background: Restorative sleep is essential for the level of cognitive performance required of truckers to drive safely. The purpose of this qualitative descriptive study was to describe and explore sleep-related and safety decision-making among truck drivers. Methods: Flyers and snowball sampling were used to recruit truck drivers into the study. Semi-structured interviews were conducted to determine personal and professional influences on sleep and safety decision-making and preferences for receiving health information. Thematic analysis was conducted to generate descriptions of participants’ experiences. Findings: The sample consisted of 10 White males with a mean of 22 years of truck-driving experience. Weather conditions and drowsiness were the most commonly described conditions that required sleep decision-making by the participants. Four themes impacting sleep- and safety-related decision-making emerged including sentinel events, evolving driver characteristics, relationships, and company-level factors. Conclusion/Application to Practice: Findings from this study suggest that there are both internal and external factors influencing sleep and safety decision-making among truck drivers. Personal relationships with important others, such as family members, and professional relationships with company dispatchers were important influences among participants. During encounters with truck drivers, occupational health nurses should assess sleep quality and quantity and review healthy sleep hygiene strategies with them and their family members, if they are available. Future larger studies are necessary to inform the development of interventions and company policies to promote healthy sleep among truck drivers.