More and more people use virtual assistants in their everyday life (e.g., on their mobile phones, in their homes, or in their cars). So-called vehicle assistance systems have evolved over the years and now perform various proactive tasks. However, we still lack concrete guidelines with all the specifics that one needs to consider to build virtual assistants that provide a convincing user experience (especially in vehicles). This research provides guidelines for designing virtual in- vehicle assistants. The developed guidelines offer a clear and structured overview of what designers have to consider while designing virtual in-vehicle assistants for a convincing user experience. Following design science research principles, we designed the guidelines based on the existing literature on the requirements of assistant systems and on the results from interviewing experts. In order to demonstrate the applicability of the guidelines, we developed a virtual reality prototype that considered the design guidelines. In a user experience test with 19 participants, we found that the prototype was easy to use, allowed good interaction, and increased the users’ overall comfort.