Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term periods of cost. Our study objective is to compare the 2- and 5-year costs associated with trimodal therapy (TMT) versus radical cystectomy (RC) benchmarked against costs for patients who received no curative treatment. Methods: This cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Medicare expenditures were summed from inpatient, outpatient, and physician services within 2 and 5 years of diagnosis to determine total costs Total Medicare costs at 2-and 5-years following TMT versus RC were compared using inverse probability of treatment-weighted (IPTW) propensity score models. Results: A total of 2,537 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 through December 31, 2009. Total median costs for patients that received no definitive/systemic treatments (RC, TMT, radiotherapy alone, or chemotherapy alone) were $73,780 vs. $88,275 at 2-and 5-years respectively. Total median costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, p<0.001) and 5-years ($424,570 vs. $253,651, p<0.001), respectively. TMT had higher outpatient median costs than RC (2-yr: $318,221 vs. $100,900; 5-yr: $367,092 vs. $146,561) with significantly higher costs largely associated with radiology, medications, pathology/laboratory, and other professional services. Conclusions: TMT vs. RC was associated with higher long-term costs among patients with muscle-invasive bladder cancer largely driven by outpatient expenditures. Reduction in costs associated with radiology, medications, pathology/laboratory, and other professional services may improve the value of TMT.