Background and ObjectivesA needleless laser‐induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser‐induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation.Patients and MethodsA 24‐week prospective, single‐center, assessor‐blinded, randomized, split‐face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser‐induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment.ResultsA single treatment of filler injection with a laser‐induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time.ConclusionsLaser‐induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.