Healthcare professionals and individuals underutilize substance use screenings, driving exploration of innovative approaches like virtual agent-guided screening. This study assessed the virtual counselor app's equivalence to in-person evaluation for substance use screening. Participants also completed a user experience questionnaire and a debriefing interview, ensuring comprehensive evaluation. The study had 204 undergraduates enrolled, all of whom underwent both virtual and in-person evaluations. Participants were randomly assigned to be administered the AUDIT-10 or DAST-10. Two one-sided t-tests indicated that the results from the screening were equivalent. This suggests that both methods produce similar results in identifying substance use. The in-person sessions were rated significantly higher for focused attention, perceived usability, and satisfaction compared to virtual counselor sessions. The debriefing interview revealed that while more people favored using the virtual counselor than not, some expressed uncertainty about utilizing it in real life. Participants' feedback on the virtual counselor platform also revealed common themes, including improving the counselor's visual presentation, enhancing the virtual environment, creating personalized interactions, modernizing visual elements, and refining audio. These findings suggest that while virtual agent-guided substance use screening is equivalent to in-person screenings in terms of accuracy, there are notable differences in user experience. Future studies should prioritize the enhancement of user experience in these applications to ensure its acceptance and integration into healthcare operations. The potential benefits of virtual screening, combined with a positive user experience, could improve the accessibility and effectiveness of substance use screening in healthcare. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]