Purpose: To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. Materials and Methods: According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE). Results: We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; I 2 =92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; I 2 =41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; I 2 =0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE). Conclusions Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.