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Background Virtual assistants can be used to deliver innovative health programs that provide appealing, personalized, and convenient health advice and support at scale and low cost. Design characteristics that influence the look and feel of the virtual assistant, such as visual appearance or language features, may significantly influence users’ experience and engagement with the assistant. Objective This scoping review aims to provide an overview of the experimental research examining how design characteristics of virtual health assistants affect user experience, summarize research findings of experimental research examining how design characteristics of virtual health assistants affect user experience, and provide recommendations for the design of virtual health assistants if sufficient evidence exists. Methods We searched 5 electronic databases (Web of Science, MEDLINE, Embase, PsycINFO, and ACM Digital Library) to identify the studies that used an experimental design to compare the effects of design characteristics between 2 or more versions of an interactive virtual health assistant on user experience among adults. Data were synthesized descriptively. Health domains, design characteristics, and outcomes were categorized, and descriptive statistics were used to summarize the body of research. Results for each study were categorized as positive, negative, or no effect, and a matrix of the design characteristics and outcome categories was constructed to summarize the findings. Results The database searches identified 6879 articles after the removal of duplicates. We included 48 articles representing 45 unique studies in the review. The most common health domains were mental health and physical activity. Studies most commonly examined design characteristics in the categories of visual design or conversational style and relational behavior and assessed outcomes in the categories of personality, satisfaction, relationship, or use intention. Over half of the design characteristics were examined by only 1 study. Results suggest that empathy and relational behavior and self-disclosure are related to more positive user experience. Results also suggest that if a human-like avatar is used, realistic rendering and medical attire may potentially be related to more positive user experience; however, more research is needed to confirm this. Conclusions There is a growing body of scientific evidence examining the impact of virtual health assistants’ design characteristics on user experience. Taken together, data suggest that the look and feel of a virtual health assistant does affect user experience. Virtual health assistants that show empathy, display nonverbal relational behaviors, and disclose personal information about themselves achieve better user experience. At present, the evidence base is broad, and the studies are typically small in scale and highly heterogeneous. Further research, particularly using longitudinal research designs with repeated user interactions, is needed to inform the optimal design of virtual health assistants.