PURPOSE: A comprehensive return on investment (ROI) calculator was developed to evaluate the monetary and nonmonetary benefits of an artificial intelligence (AI)-powered radiology diagnostic imaging platform to inform decision makers interested in adopting AI. METHODS: A calculator was constructed to calculate comparative costs, estimated revenues, and quantify the clinical value of using an AI platform compared with no use of AI in radiology workflows of a US hospital over a 5-year time horizon. Parameters were determined on the basis of expert interviews and a literature review. Scenario and deterministic sensitivity analyses were conducted to evaluate calculator drivers. RESULTS: In the calculator, the introduction of an AI platform into the hospital radiology workflow resulted in labor time reductions and delivery of an ROI of 451% over a 5-year period. The ROI was increased to 791% when radiologist time savings were considered. Time savings for radiologists included more than 15 8-hour working days of waiting time, 78 days in triage time, 10 days in reading time, and 41 days in reporting time. Using the platform also provided revenue benefits for the hospital in bringing in patients for clinically beneficial follow-up scans, hospitalizations, and treatment procedures. Results were sensitive to the time horizon, health center setting, and number of scans performed. Among those, the most influential outcome was the number of additional necessary treatments performed because of AI identification of patients. CONCLUSIONS: The authors demonstrate a substantial 5-year ROI of implementing an AI platform in a stroke management-accredited hospital. The ROI calculator may be useful for decision makers evaluating AI-powered radiology platforms.