BACKGROUND Trimodal therapy (TMT) is a suitable alternative to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC). In this study, we conducted a cost-effectiveness evaluation of RC±NAC vs. TMT for MIBC in the universal and publicly funded Canadian healthcare system. METHODS We developed a Markov model with Monte-Carlo microsimulations. Rates and probabilities of transitioning within different health states (e.g., cure, locoregional recurrence, distant metastasis, death) were input in the model after a scoped literature review. Two main scenarios were considered: 1) academic center; and 2) populational-level. Results were reported in life-years gained (LYG), quality-adjusted life years (QALY), and incremental cost-effectiveness ratio (ICER). A sensitivity analysis was performed. RESULTS A total of 20 000 patients were simulated. For the academic center model, TMT was associated with increased effectiveness (both in LYG and QALY) at a higher cost compared to RC±NAC at five and 10 years. This resulted in an ICER of $19 746/QALY per patient undergoing the TMT strategy at 10 years of followup. For the populational-level model, RC±NAC was associated with higher effectiveness at 10 years, with an ICER of $3319/QALY per patient. This study was limited by heterogeneity within the studies used to build the model. CONCLUSIONS In this study, TMT performed in academic centers was cost-effective compared to RC±NAC, with higher effectiveness at a higher cost. On the other hand, RC±NAC was considered cost-effective compared to TMT at the populational-level. Further studies are needed to confirm these results.