Purpose: Neuromodulator injection is the most commonly performed cosmetic procedure worldwide. As new formulations of botulinum toxin type A become commercially available, generating data on the clinical comparability between products is important. Here, the author compared the onset of action of prabotulinumtoxinA (Pra-B) and onabotulinumtoxinA (Ona-B) in the treatment of forehead and lateral canthal rhytids. Methods: A randomized, controlled, split-face pilot study was conducted on 5 subjects with mild to severe forehead and lateral canthal rhytids. All subjects were administered Pra-B and Ona-B injections to the forehead and periorbital region in a randomized, split-face manner. Toxin preparation, units administered, injection sites, and assessment timing were controlled. Subjects were assessed at baseline (day 0) and post-treatment at days 1, 2, 3, 4, 5, 6, and 7 using a validated 5-point Wrinkle Severity Scale (WSS; 0 = no lines, 4 = very severe lines). Standardized videography of subjects at rest and at maximal contraction was obtained at days 0, 1, 2, 3, 4, 5, 6 and 7 or until scale stability was achieved. Subject- and investigator-assessed WSS scores were reported. Primary end point was response onset (the time to improve by ≥1 point on the WSS) as defined by investigator assessment at maximal contraction. Results: 5 subjects (3 women, 2 men) with a mean age of 46.2 years (range, 29-69 years) were treated. Baseline mean score at maximal contraction was 2.8 for forehead rhytids (range, 1-4) and 2.0 for lateral canthal rhytids (range, 1-3) as assessed by investigator. Mean time of onset when treating the frontalis was 3.4 days for Ona-B and 3.2 days for Pra-B. Mean time of onset when treating the orbicularis oculi was 3.0 days for Ona-B and 2.2 days for Pra-B. At the time of response onset, Ona-B demonstrated a mean improvement of 1.2 points (frontalis) and 1.2 points (orbicularis oculi). Pra-B demonstrated a mean improvement of 1.3 points (frontalis) and 1.0 points (orbicularis oculi). Conclusion: Preliminary results from this pilot study suggest comparable time of onset and efficacy when treating the frontalis and orbicularis oculi with onabotulinumtoxinA and prabotulinumtoxinA injection.