OBJECTIVES: Antimuscarinics are oral treatment options for overactive bladder (OAB) that reduce symptoms and improve patients’ quality of life. Antimuscarinics are generally well tolerated, but differences in their efficacy and tolerability profiles have been observed. Solifenacin and fesoterodine are among the newest antimuscarinics. This analysis assessed the cost effectiveness of solifenacin and fesoterodine, the most recently approved antimuscarinics, from the US private payer and Medicare Advantage perspectives. METHODS: A Markov cost-effectiveness model was developed to simulate OAB course, management, and adverse effects of OAB treatment in simulated cohorts of patients over a 3-year time horizon. Incontinence and micturition average daily frequencies were stratified in five bands: incontinence (0, >0-1, >1-2, >2-3, >3), micturitions (≥8, >8-10, >10-12, >12-14, >14). Transition probabilities between bands were derived from a mixed treatment comparison. Therapy began with an oral OAB agent, followed by switch to another oral OAB agent or discontinuation. Tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA were third-line treatments. EQ-5D equivalent utilities were mapped from demographics, incontinence, and micturition frequencies. OAB-related comorbidities and treatment-related adverse events triggered utility decrements and added costs. The primary outcome was cost per quality-adjusted life year (QALY). Secondary outcomes were costs per strata improvement in incontinence and micturition. One-way and probabilistic sensitivity analyses were performed. RESULTS: Incremental costs per QALY for solifenacin were US$44,954 and US$45,656 from the private payer and Medicare Advantage perspectives, respectively. The incremental costs per incontinence and micturition strata improvement for solifenacin were US$ 10,048 and US$6,200 from the private payer perspective and US$9,402 and US$5,953 from the Medicare Advantage perspective, respectively. Based on a willingness-to-pay threshold of US$50,000 per QALY, solifenacin was cost-effective in 77% of probabilistic samples. CONCLUSIONS: Results suggest that compared to fesoterodine, solifenacin is a cost-effective antimuscarinic option for treatment of OAB from US private payer and Medicare Advantage perspectives.