Abstract Context Botulinum toxin A (BoNTA) has received regulatory approval for use in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), but it remains unlicensed in other lower urinary tract symptoms (LUTS) indications such as nonneurogenic LUTS in men with benign prostatic enlargement (LUTS/BPE), bladder pain syndrome (BPS), and detrusor sphincter dyssynergia (DSD). Objective To compare statistically the outcomes of high level of evidence (LE) studies with placebo using BoNTA for LUTS indications; NDO, OAB, LUTS/BPE, BPS and DSD. Evidence acquisition We conducted a systematic review of the published literature on PubMed, Scopus, and Embase reporting on BoNTA use in LUTS dysfunction. Statistical comparison was made between high LE studies with placebo and low LE studies. Evidence synthesis In adult NDO, there are significantly greater improvements with BoNTA in daily incontinence and catheterisation episodes (−63% and −18%, respectively; p < 0.01), and the urodynamic parameters of maximum cystometric capacity (MCC), reflex volume, and maximum detrusor pressure (MDP) (68%, 61%, and −42%, respectively; all p < 0.01). In OAB, BoNTA leads to significant improvements in bladder diary parameters such as daily frequency (−29%), daily urgency (−38%), and daily incontinence (−59%) (all p < 0.02). The urodynamic parameters of MCC and MDP improved by 58% ( p = 0.04) and −29% ( p = 0.002), respectively. The risk of urinary tract infection was significantly increased from placebo at 21% versus 7% ( p < 0.001), respectively; the risk of intermittent self-catherisation increased from 0% to 12% ( p < 0.001). Men with LUTS/BPE showed no significant improvements in International Prostate Symptom Score, maximum flow rate, or prostate volume. There were insufficient data for statistical analysis in DSD, BPS, and paediatric studies. Low LE studies were found to overestimate the effects of BoNTA in all indications, but differences from high LE studies were significant in only a few parameters. Conclusions BoNTA significantly improves all symptoms and urodynamic parameters in NDO and OAB. The effect of BoNTA in treating LUTS dysfunction appears to be overestimated in lower as opposed to higher LE studies.