Maximizing patient comfort during hyaluronic acid gel injection is a common concern that is usually addressed by selecting fillers containing lidocaine. Around 2 randomized, double-blinded, split-face trials aimed to establish the noninferiority of particular hyaluronic acid fillers integrating mepivacaine (RHA-M) into their lidocaine controls at delivering pain relief. Around 30 patients in each experiment received injections of RHAR-M versus RHAR, and RHA4-M versus RHA4, respectively, in the perioral rhytids (PR) and nasolabial folds (NLF). The pain was assessed on a visual analog scale; aesthetic effectiveness was evaluated with established scales, and safety was tracked based on common treatment responses (CTRs) and adverse events (AEs). RHA-M fillers demonstrated as efficacious as their lidocaine equivalents at reducing pain (noninferior, P<.0002 and P<.0001). Bilateral wrinkle improvement was observed both in the PR (−1.5 ± 0.6 points on each side) and in the NLF (−1.8 ± 0.6 and −1.9 ± 0.5 points) trials at one month, with practically comparable responder rates (≥96.7%). Common treatment reactions and AEs were similar between treated sides, and none was clinically noteworthy. Resilient hyaluronic acid fillers with either mepivacaine or lidocaine are as effective in reducing pain during treatment and are similarly performant and safe for repairing dynamic facial wrinkles and folds.