OBJECTIVES: Non-muscle invasive bladder cancer (NMIBC) is a complex disease with wide variation in risks of recurrence and progression, treatment efficacy and complications, and patient co-morbidities.  To assist in medical decision making from clinical and cost perspectives, we have developed a simulation model that synthesizes the evidence on NMIBC using the Archimedes Model platform. METHODS: The NMIBC model consists of a patient generation component in which virtual patients are constructed from SEER case listings; a natural history component that captures recurrence, progression, and bladder cancer mortality; a health care component that captures the effects of treatments, tests, and surveillance; and a cost component that tracks the costs relevant to bladder cancer care. Using this model, we performed a 5-year virtual clinical trial of 350 NMIBC patients with demonstrated Bacillus Calmette-Guerin failure, randomized to either immediate cystectomy or conservative treatment with Mitomycin C (MMC) intravesical therapy. The model is integrated within the Archimedes Model platform, which captures the effects of both NMIBC and patient co-morbidities. This model, validated against 5 published studies, gives recurrence and progression rates within ±20% of published results (Figure 1). RESULTS: The virtual clinical trial shows a 5-yr cystectomy rate of 51% in the MMC arm, with an average delay to cystectomy of 0.84 yr (median 0.44 yr). The immediate cystectomy arm saves 0.26 life years (LY) and $5,598 in total bladder cancer cost per patient compared to the MMC arm. CONCLUSIONS: We have constructed a dynamic, quantitative model of NMIBC that can predict clinical and economic outcomes and help optimize treatment and surveillance guidelines. The virtual clinical trial quantifies LY and cost outcomes for immediate cystectomy versus conservative therapy, and provides a valuable tool for trial design and health economic analyses.