PURPOSE:One quarter of patients will not respond to initial intra-detrusor Botulinum toxin A (BTX) injections for detrusor overactivity. Alternative treatment options include long-term catheterization, sacral neuromodulation, urinary diversion or bladder augmentation. Some of these procedures are invasive. This review explores modifications to BTX delivery that can improve outcome. METHODS:A search of Medline, Embase and Cochrane Library to December 2017 was performed according to Preferred Reporting Items for Systematic Review and Metaanalysis (PRISMA) guidelines. Search criteria included, dose escalation, increasing injection site number, trigone injection, switching preparation and alternative methods of BTX delivery. RESULTS:Several modifications to BTX delivery may improve response. There is moderate evidence that increasing the dose from 100 U to 200 U results in statistically better symptom control. Trigone-including injections were associated with significantly improved patient-reported symptom scores, as well as superior results in urodynamic outcomes without risking urinary retention and vesico-ureteric reflux. Switching from onabotulinum (OTA) or abobotulinum (ATA) or vice versa may also improve response in over 50% of patients as shown in limited studies. Increasing the number of injection sites is not beneficial. Indeed, decreasing the number of injections to as low as three sites does not result in decreased clinical outcomes. Injection-free delivery is associated with lower efficacy compared to conventional intradetrusor injections. CONCLUSION:Before contemplating alternative treatments, practitioners can try to improve on BTX delivery. Firstly, the dose can be increased to 200 U; the trigone included in the injection sites and switching brands may also be helpful.