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OBJECTIVE To prospectively evaluate the effectiveness of OnabotulinumtoxinA (BTX-A) on neurogenic overactive bladder (nOAB) in adults with congenital spinal dysraphism (CSD). SUBJECTS AND METHODS We conducted a prospective, nonrandomized pilot study of 24 adults with CSD and nOAB. Patients were evaluated with baseline video-urodynamics (UDS) and validated questionnaires, underwent injection 200U BTX-A, and then underwent repeat evaluation with questionnaires and UDS 1-3 months post injection. A high-risk subgroup was separately analyzed based on adverse clinical characteristics (i.e. decrease bladder compliance, vesicoureteral reflux, hydronephrosis, chronic kidney disease). RESULTS BTX-A injection improved patient recorded outcome measures seen in both I-QOL Score total (67.9 vs 75.5, p= 0.007) and Neurogenic Bladder Symptom Score total (38.0 vs 29.0, p=0.001). On UDS, BTX-A injection significantly improved end filling pressure (16.0 vs 8.8, p= 0.036) and also improved bladder compliance (mL/cm H2O) (89.38 vs 135.81, p= 0.445). High-risk patients were found to have similar improvements in most subjective questionnaire scoring, a significant decrease in end filling pressures, and improved bladder compliance on UDS. CONCLUSION BTX-A can be used as an effective treatment in adults with CSD. We found that BTX-A significantly improved quality of life from patient reported outcome measurements as well as improving end filling pressures and bladder compliance. These improvements were seen even within our high-risk subgroup. Further studies are needed to evaluate long-term efficacy and appropriate follow-up of this at-risk population.