Antimicrobial resistance (AMR) is a global health threat. This randomized controlled trial evaluates the impact of experiential virtual reality (VR) versus information provision via VR or leaflet on prudent antibiotic use. A total of 249 (239 analyzed) participants were randomized into three conditions: VR Information + Experience, VR Information, or Leaflet Information. All participants received AMR information, while those in the VR Information + Experience condition additionally engaged in a game, making treatment decisions for their virtual avatar’s infection. Participants in the VR Information + Experience condition showed a significant increase in prudent use intentions from baseline (d = 1.48). This increase was significantly larger compared to the VR Information (d = 0.50) and Leaflet Information (d = 0.79) conditions. The increase in intentions from baseline remained significant at follow-up in the VR Information + Experience condition (d = 1.25). Experiential VR communication shows promise for promoting prudent antibiotics use.