OBJECTIVES: Patients with overactive bladder (OAB) who have failed an oral therapy have a number of treatment options including onabotulinumtoxinA (onabotA) injection, percutaneous tibial nerve stimulation (PTNS), or implantable sacral neurostimulation (SNS) device. This analysis estimates the cost-effectiveness of onabotA 100U compared to PTNS and SNS from the US payer perspective. METHODS: A Markov health state transition model was developed with 3-month cycles and health states based on daily urinary incontinence episodes (UIE). Patients were treated with either onabotA, PTNS, or SNS. Those who discontinued therapy transitioned to best supportive care. Individual patient level data from phase 3 and longterm extension studies informed efficacy and safety data for onabotA. Published literature informed safety and efficacy for PTNS and SNS. Resource utilization and unit cost data were obtained from published sources and expert opinion. Outcomes were expressed in 2014 USD ($) per Quality Adjusted Life Years (QALYs, measured by I-QOL mapped to EurQoL-5D). A 10-year time horizon and discount rate of 3.0% was applied. Parameter uncertainty was investigated using deterministic and probabilistic sensitivity analyses (PSA). RESULTS: For the base case, total costs over 10 years were $13,030 for onabotA, $12,239 for PTNS, and $37,735 for SNS; total QALYs gained were 7.179, 7.106, and 7.130, respectively, yielding an incremental cost effective ratio (ICER) of $10,848 for onabotA vs PTNS; onabotA was dominant against SNS. PSAs demonstrated that onabotA had an 8% or 66% probability of being dominant and 70% or 68% likelihood of being below $100,000 cost-effectiveness threshold compared to PTNS and SNS, respectively. CONCLUSIONS: This analysis shows that OnabotA is a cost-effective therapy for OAB compared with PTNS and SNS. On grounds of its cost effectiveness, onabotA should be considered a treatment of choice among patients who have failed ≥1 anticholinergic.