BackgroundBotulinum neurotoxin type A (BoNT‐A) is well‐established for treatment of glabellar lines (GLs), and mostly formulated as powders requiring reconstitution for injection. The approved liquid formulation, ready‐to‐use (RTU) abobotulinumtoxinA was developed to ease injection procedures and prevent reconstitution errors. This multicenter, open‐label, Phase IV study evaluated GL treatment experience using RTU abobotulinumtoxinA versus powder BoNT‐A (onabotulinumtoxinA).MethodsFemales with experience of BoNT‐A facial treatment were randomized 2:1 to GL treatment with 50 U RTU abobotulinumtoxinA (N = 99) or 20 U powder BoNT‐A (N = 51) and followed‐up for 6 months or 1 month, respectively. Assessments included: time to prepare each product for injection (primary endpoint); investigators' experience with product preparation/reconstitution; investigators' and subjects' treatment experience; safety; and for the RTU product: aesthetic improvement of GLs; subject satisfaction.ResultsCompared with powder BoNT‐A, RTU abobotulinumtoxinA required statistically significantly less preparation time (mean 0:33 vs. 1:34 min: s; p < 0.0001). Investigators preferred RTU abobotulinumtoxinA over powder BoNT‐A (81% of treatment sessions) and found it allowed more time to communicate with subjects (97%). All investigators (100%) also found it easy‐to‐use, easy‐to‐learn, and that it fulfilled their expectations. Subjects found the RTU abobotulinumtoxinA treatment comfortable (91%), and through 6 months posttreatment, most reported satisfaction with their appearance (≥88%), looking natural (≥95%) and refreshed (≥80%). At Month 1, 99% of RTU‐treated subjects had investigator‐assessed improved aesthetic appearance in GLs, maintained in 76% at Month 6. No serious adverse events occurred.ConclusionRTU abobotulinumtoxinA for GL treatment is well‐tolerated, efficacious, shows high levels of subject satisfaction throughout 6 months, saves time, and is preferred by clinicians over powder BoNT‐A.ClinicalTrials.gov RegistryNCT05277337.