OBJECTIVES: Urinary incontinence (UI) secondary to a neurogenic pathology, including spinal cord injury (SCI) and Multiple Sclerosis (MS), is termed neurogenic detrusor overactivity (NDO). Patients with NDO experience a decrease in quality of life (QoL) and are at risk for upper urinary tract damage. We sought to investigate the clinical and economic impact of onabotulinumtoxinA treatment for UI due to NDO from the US payer perspective. METHODS: We developed a Markov state transition model to estimate outcomes and costs for anticholinergic refractory NDO patients who received onabotulinumtoxinA or best supportive care (BSC). Non-responding patients (<50% reduction in UI episodes at 6 weeks) were eligible to receive invasive procedures (i.e. augmentation cystoplasty or sacral neuromodulation).  Patients could transition through six health states defined by response to initial treatment, invasive procedures, and death.  Time in each health state was adjusted for patient QoL and summed to estimate quality-adjusted life years (QALY).  We included direct medical costs related to medications and invasive treatments, physician visits, and catheterization.  Outcomes and costs were compared using the incremental cost-effectiveness ratio.  The time horizon of the model was 3 years and results were discounted at 3%. RESULTS: OnabotulinumtoxinA increased QALYs by 0.059 and costs by $1,466 compared to best supportive care, yielding an estimated ICER of $24,720/QALY. OnabotulinumtoxinA also decreased mean incontinence episodes per person-year by 400, resulting in a cost of $4 per incontinence episode avoided. Model results were most sensitive to the probability of treatment response.  The probabilistic sensitivity analysis indicated that at a willingness to pay of $50,000/QALY, onabotulinumtoxinA has a 97% probability of being cost-effective.  In subgroup analyses of each etiology, onabotulinumtoxinA yielded an ICER of $32,268/QALY in MS and $2,182 in SCI.  CONCLUSIONS: OnabotulinumtoxinA appears to be a cost-effective intervention for UI due to NDO when compared to best supportive care.